A novel acropectoral syndrome maps to chromosome 7q36

Original Article
Munis Dundar, Tilda M Gordon, Irfan Ozyazgan, Fahri Oguzkaya, Yusuf Ozkul, Alexander Cooke, A Graham Wilkinson, Susan Holloway, Frances R Goodman, John L Tolmie
J Med Genet 2001;38:304-309

F syndrome (acropectorovertebral syndrome) is a dominantly inherited skeletal dysplasia affecting the hands, feet, sternum, and lumbosacral spine, which has previously been described in only two families. Here we report a six generation Turkish family with a related but distinct dominantly inherited acropectoral syndrome. All 22 affected subjects have soft tissue syndactyly of all fingers and all toes and 14 also have preaxial polydactyly of the hands and/or feet. In addition, 14 have a prominent upper sternum and/or a blind ending, inverted U shaped sinus in the anterior chest wall. Linkage studies and haplotype analysis carried out in 16 affected and nine unaffected members of this family showed that the underlying locus maps to a 6.4 cM interval on chromosome 7q36, between EN2and D7S2423, a region to which a locus for preaxial polydactyly and triphalangeal thumb-polysyndactyly has previously been mapped. Our findings expand the range of phenotypes associated with this locus to include total soft tissue syndactyly and sternal deformity, and suggest that F syndrome may be another manifestation of the same genetic entity. In mice, ectopic expression of the geneSonic hedgehog(Shh) in limb buds and lateral plate mesoderm during development causes preaxial polydactyly and sternal defects respectively, suggesting that misregulation ofSHH may underlie the unusual combination of abnormalities in this family. A recently proposed candidate gene for 7q36 linked preaxial polydactyly is LMBR1, encoding a novel transmembrane receptor which may be an upstream regulator of SHH.

Progress towards the 'Golden Age' of Biotechnology

Review
K. M. A. Gartland, F. Bruschi, M. Dundar, P. B. Gahan, M. P. Viola Magni, Y. Akbarova
Current Opinion in Biotechnology. 24: S6-S13.

Biotechnology uses substances, materials or extracts derived from living cells, employing 22 million Europeans in a euro 1.5 Tn endeavour, being the premier global economic growth opportunity this century. Significant advances have been made in red biotechnology using pharmaceutically and medically relevant applications, green biotechnology developing agricultural and environmental tools and white biotechnology serving industrial scale uses, frequently as process feedstocks. Red biotechnology has delivered dramatic improvements in controlling human disease, from antibiotics to overcome bacterial infections to anti-HIV/AIDS pharmaceuticals such as azidothymidine (AZT), anti-malarial compounds and novel vaccines saving millions of lives. Green biotechnology has dramatically increased food production through Agrobacterium and biolistic genetic modifications for the development of ‘Golden Rice’, pathogen resistant crops expressing crystal toxin genes, drought resistance and cold tolerance to extend growth range. The burgeoning area of white biotechnology has delivered bio-plastics, low temperature enzyme detergents and a host of feedstock materials for industrial processes such as modified starches, without which our everyday lives would be much more complex. Biotechnological applications can bridge these categories, by modifying energy crops properties, or analysing circulating nucleic acid elements, bringing benefits for all, through increased food production, supporting climate change adaptation and the low carbon economy, or novel diagnostics impacting on personalized medicine and genetic disease. Cross-cutting technologies such as PCR, novel sequencing tools, bioinformatics, transcriptomics and epigenetics are in the vanguard of biotechnological progress leading to an ever-increasing breadth of applications. Biotechnology will deliver solutions to unimagined problems, providing food security, health and well-being to mankind for centuries to come.

A Study of CDKL5 Gene Mutations in Pediatric Patients with Persistent Seizure, Autistic Disorder and Seizure in Addition to Autistic Disorder During Infancy and Early Childhood

Abstract
Murat Erdogan, Asli Subasioglu Uzak, Didem Behice Oztop, Hakan Gumus, Munis Dundar
Current Opinion in Biotechnology. 24: S100-S100.

A case with 49, XXXXY syndrome: rare chromosomal aneuploidies

Abstract
Murat Erdogan, Asli Subasioglu Uzak, Sevda Yesim Karabulut, Oguzhan Bahadir, Fatma Colak, Muhammed Ensar Dogan, Burhan Balta, Cetin Saatci, Munis Dundar
Current Opinion in Biotechnology. 22: S106-S106.

Partial trisomy 14q due to maternal t(4;14)(p16;q32) in a dysmorphic newborn

Case Report
M. Dundar, A. Uzak, C. Saatci, H. Akalin
Genetic Counseling. 22: 287-292.

Partial Trisomy 14q is a rare chromosomal disorder that mostly results from a parental translocation. We report here a newborn boy with partial trisomy 14q and dysmorphic features that are compatible with previously reported cases. Conventional cytogenetic analysis revealed an extra chromosomal segment at the end of the short arm of chromosome 4. In order to determine the origin of this chromosome region we used subtelomeric FISH technique. Based on the results of these cytogenetic studies and the physical examination, this dysmorphic case was diagnosed as partial trisomy of 14q and his karyotype determined as 46 XY, der(4)t(4;14)(p16;q32) resulting from a balanced maternal translocation identified as 46,XX, t(4;14)(p16;q32).

Partial trisomy 3q in a child with sacrococcygeal teratoma and cornelia de lange syndrome phenotype

Case Report
M. Dundar, A. Uzak, M. Erdogan, C. Saatci, S. Akdeniz, G. Luleci, I. Keser, S. Karauzum
Genetic Counseling. 22: 199-205.

Partial duplication of 3q is a rare chromosomal disorder that leads to multiple congenital abnormalities such as growth retardation, microcephaly and characteristic facial features. Although the phenotype of the patient has similarities with Cornelia de Lange Syndrome they are etiologically different. We report here a 9 months old baby boy with partial duplication of 3q and features similar with Cornelia De Lange syndrome. Conventional cytogenetic analysis revealed a derivative chromosome 21. In order to determine the origin of this chromosome region we used subtelomeric FISH technique. Based on the results of all these cytogenetic studies and the physical examinations, the diagnosis is partial 3q duplication.

Frank-ter Haar syndrome with unusual clinical features

Abstract
Munis Dundar, Cetin Saatci, Sener Tasdemir, Mustafa Akcakus, Ahmet Okay Caglayan, Yusuf Ozkul
European Journal of Medical Genetics. 52: 247-249.

Frank-ter Haar syndrome first recognized by Frank et al. [Y. Frank, M. Ziprkowski, A. Romano, R. Stein, M.B. Katznelson, B. Cohen, R.M. Goodman, Megalocornea associated with multiple skeletal anomalies: a new genetic syndrome?, J. Genet. Hum. 21 (1973) 67–72.] and subsequently confirmed by ter Haar et al. [B. Ter Haar, B. Hamel, J. Hendriks, J. de Jager, Melnick–Needles syndrome: indication for an autosomal recessive form, Am. J. Med. Genet. 13 (1982) 469–477.]. The main clinical features of the syndrome are brachycephaly, wide fontanels, prominent forehead, hypertelorism, prominent eyes, macro cornea with or without glaucoma, full cheeks, small chin, bowing of the long bones, and flexion deformity of the fingers [S.M. Maas, H. Kayserili, J. Lam, M.Y. Apak, R.C. Hennekam, Further delineation of Frank-ter Haar syndrome, Am. J. Med. Genet. 131 (2004) 127–133.]. We report a child with Frank-ter Haar syndrome presenting unusual clinical features. Hypopigmented areas in hair, bilateral adducted thumb, bilateral contractures in elbows and pelvic limb, atrial septal defect have not been described previously in the literature. Our patient also had double-outlet right ventricle.

A case with Waardenburg syndrome presenting with two separate translocations - one reciprocal and one complex

Case Report
M. Dundar, G. Lowther, J. Colgan, Y. Ozkul, Z. Candemir, C. Saatci, S. Kurtoglu, J. Watt, N. Morrison
Clinical Dysmorphology. 10: 65-66.

A 2-month-old Turkish male with Waardenburg syndrome who has two de novo translocations is described. The translocations are a reciprocal translocation between chromosomes 1 and 8, and a more complex translocation involving chromosomes 4 and 7.

A case with adducted thumb and club foot syndrome

Case Report
M. Dundar, S. Kurtoglu, B. Elmas, F. Demiryilmaz, Z. Candemir, Y. Ozkul, A. C. Durak
Clinical Dysmorphology. 10: 291-293.

Unbalanced 3;22 Translocation With 22q11 and 3p Deletion Syndrome

Abstract
Munis Dundar, Aslihan Kiraz, Sener Tasdemir, Hilal Akalin, Selim Kurtoglu, Filiz Hafo, Naci Cine, Hakan Savli
American Journal of Medical Genetics Part A. 152A: 2791-2795.

This report describes a 25-day-old Turkish boy with unbalanced 3;22 translocation that includes the 22q11.2 deletion and 3p25 deletion syndrome. The karyotype was 45, XY,der(3)t(3;22)(p25;q11),-22. Although no immunological dysfunction could be demonstrated, the boy presented some manifestations of DiGeorge anomaly (DGA), which has been associated with monosomy for the same region of chromosome 22, velocardiofacial syndrome (VCFS), and the 3p deletion syndrome. Clinical features include short stature, hypertelorism, low set ears, cleft lip with cleft palate, short neck, truncus arteriosus, micropenis, clubfoot, over riding toes on right foot, four digits on left foot and growth delay. In addition he had feeding difficulties, respiratory infections, and developmental delay. Fluorescence in situ hybridization (FISH) studies confirmed loss of the proximal DiGeorge chromosomal region (DGCR). Array CGH analysis showed the deletion sites on chromosomes 3 and 22. This report documents a rare chromosomal aberration that causes the 22q11 and 3p deletion syndrome simultaneously.

A molecular analysis of familial Mediterranean fever disease in a cohort of Turkish patients

Original Article
Munis Dundar, Aslihan Kiraz, Elif Funda Emirogullari, Cetin Saatci, Serpi Taheri, Mevlut Baskol, Seher Polat, Yusuf Ozkul
Annals of Saudi Medicine. 32: 343-348.

BACKGROUND AND OBJECTIVES: Familial Mediterranean fever (FMF) is an autosomal recessive disorder caused by mutations in MEFV gene, which encodes pyrin. FMF is especially prevalent among Turks, Armenians, non-Ashkenazi Jews, and Arabs. The aim of this study was to determine the frequency and spectrum of 12 MEFV mutations of these patients and any genotype-phenotype correlation in this large Turkish group.

DESIGN AND SETTING: A retrospective study at Erciyes University Medical Faculty, from January 2007 to June 2009.

PATIENTS AND METHODS: We enrolled 446 Turkish FMF patients and identified the known 12 MEFV mutations with clinical investigations. DNA was amplified by PCR and subjected to reverse hybridization for the detection of MEFV gene mutations. RESULTS: Among the 446 patients, 103 (46.6%) had a heterozygous genotype, 44 (19.9%) had a homozygous genotype, and 74 (33.49%) had a compound heterozygous genotype. The most common mutation detected was heterozygote M694V (46/221). Of the included 446 patients, 218 (48.87%) were male and 228 (51.12%) were female. High parental consanguinity rates affect FMF development. The clinical spectrum varied with different mutation profiles.

CONCLUSIONS: This study plays an important role in detecting the distribution of MEFV mutations and determining clinical approaches among Turk FMF patients. Also, we seemed to detect a distinctive clinical picture, specifically a lower frequency of amyloidosis.

A case of ambiguous genitalia presenting with a 45,X/46,Xr(Y)(p11.2;q11.23)/47,X,idic(Y)(p11.2),idic(Y)(p11.2) karyotype

Case Report
M. Dundar, G. Lowther, H. Acar, S. Kurtoglu, F. Demiryilmaz, M. Kucukaydin
Annales De Genetique. 44: 5-8.

An infant with ambiguous genitalia was found to have a karyotype 45,X/46,X,r(Y)(p11.2;q11.23)/47,X,idic(Y)(p11.2),idic(Y)(p11.2) using G-banding, C-banding and FISH. Examination of the genitalia revealed a phallus measuring 1.5 cm in length and 0.5 cm wide with perineal orifice. Subtle phenotypic features consistent with Turner syndrome were not present. Genital ultrasonography revealed the presence of an infantile uterus. Endoscopy of the vagina, uterus and cervix appeared normal.

The role of TNF-alpha and PAI-1 gene polymorphisms in familial Mediterranean fever

Original Article
Munis Dundar, Aslihan Kiraz, Burhan Balta, Elif Funda Emirogullari, Gokmen Zararsiz, Alper Yurci, Duran Aslan, Mevlut Baskol
Modern Rheumatology. 23: 140-145.

OBJECTIVES: Familial Mediterranean fever (FMF) is one of the most serious inherited inflammatory disorders among Jewish, Armenian, Turkish and Arab populations. The imbalance between pro- and anti-inflammatory cytokines may play a role in its etiology. We have investigated whether tumor necrosis factor-alpha (TNF-alpha) and plasminogen activator inhibitor 1 (PAI-1) gene polymorphisms are associated with FMF and evaluated the relationship between these polymorphisms and genotypic manifestation of FMF.

METHODS: We investigated single nucleotide polymorphisms of the TNF-alpha promoter at positions -308 G/A and the PAI-1 4G/5G gene polymorphism in peripheral blood leukocytes collected from 177 individuals with FMF with different genotype combinations. All of the polymorphisms of TNF-alpha and PAI-1 were detected by PCR and restriction fragment length polymorphism analysis.

RESULTS: There were no association between the TNF-alpha/308 genotypes and mutations in FMF. In contrast, the PAI-1 4G/5G gene polymorphism may have a significant effect in FMF disease.

CONCLUSIONS: Screening with PAI-1 gene polymorphism tests may be beneficial for tracing future FMF patients. However, further investigations are needed to reach a conclusion on the association between PAI-1 polymorphisms and FMF.

Congenital alacrima in a patient with G (Opitz frias) syndrome

Case Report
M. Dundar, K. Erkilic, F. Demiryilmaz, M. Kucukaydin, M. Kendirci, H. Okur, A. Kazez
Human Genetics. 97: 540-542.

Congenital alacrima is an autosomal dominant disorder showing markedly deficient lacrimation and punctate corneal epithelial erosions. The G (Opitz-Frias) syndrome is also an autosomal dominant disorder characterised by hypertelorism, hypospadias, stridor, and dysphagia. Here we report a 5-year-old boy with the G syndrome presenting congenital alacrima.

Common Familial Mediterranean Fever gene mutations in a Turkish cohort

Original Article
Munis Dundar, Elif Funda Emirogullari, Aslihan Kiraz, Serpil Taheri, Mevlut Baskol
Molecular Biology Reports. 38: 5065-5069.

Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disorder with the responsible gene of MEFV which primarily affects Jewish, Armenian, Turkish and Arab populations. The FMF gene (MEFV) has recently been cloned to chromosome 16p, which encodes pyrin. In the present study, we enrolled 2,067 unrelated patients with the suspicion of FMF in Middle Anatolia between the years 2006–2009 and identified the 12 MEFV mutations. DNA was amplified by PCR and subjected to reverse hybridization for the detection of MEFV gene mutations. Among the 2,067 patients, 866 (41.9%) were males and 1,201 (58.1%) were females. The mutations were homozygous in 176 (16.85%) patients, compound heterozygous in 314 (30.1%) patients, heterozygous in 546 (52.25%) patients and the other forms of mutations were found in 8 patients (0.76%). No mutation was detected in 1,023 (49.5%) patients. The most frequent mutations were M694V, M680I (G/C), E148Q and V726A. We could not find any significant differences between the two common mutations according to the gender. The high incidence of MEFV gene mutations in the Turkish population indicated that newborn screening may be discussed in the future. Because of the ethnic origin of Anatolia, larger serial analyses are necessary to investigate the rate and coexistence of these mutations.

An autosomal recessive adducted thumb club foot syndrome observed in Turkish cousins

Case Report
M. Dundar, S. Ceylaner, G. Ceylaner
Clinical Genetics. 51: 61-64.

Male and female cousins, the offspring of consanguineous Turkish parents, have been affected by a hitherto unreported combination of problems comprising moderate to severe psychomotor developmental delay, ocular anterior chamber abnormality, facial dysmorphisms (broad, bossed forehead, late-closing fontanelle, telecanthus, downslanting palpebral fissures, posteriorly rotated ears, downturned angles of mouth), arachnodactyly and distal arthrogryposis with severely adducted thumbs and club feet. This striking phenotype has some similarities with the multiple pterygium syndrome (Escobar syndrome), but it most likely represents a distinct condition caused by an autosomal recessive gene defect.

How the I1307K adenomatous polyposis coli gene variant contributes in the assessment of risk of colorectal cancer, but not stomach cancer, in a Turkish population

Original Article
Munis Dundar, Ahmet Okay Caglayan, Cetin Saatci, Hatice Karaca, Mevlut Baskol, Serpil Tahiri, Yusuf Ozkul
Cancer Genetics and Cytogenetics. 177: 95-97.

Germline and somatic truncating mutations of the adenomatous polyposis coli gene (APC) are thought to initiate colorectal tumor formation in familial adenomatous polyposis syndrome and sporadic colorectal carcinogenesis, respectively. Recently, an isoleucine-lysine polymorphism at codon 1307 (I1307K) of the APC gene has been identified in 6-7% of the Ashkenazi Jewish population. To assess the risk of this common APC allelic variant in colorectal carcinogenesis, a cohort of unselected Turkish subjects with stomach or colorectal cancer (or both) was analyzed for the APC I1307K polymorphism. Genomic DNA was extracted from patients by obtaining all stomach and colon malign polipose tissues using nuclei lysis methods. Detection of the I1307K mutation was performed using the commercial Pronto APC kit according to the manufacturer’s instructions. The APC I1307K allele was identified in 7 of 57 stomach carcinoma patients (12.3%; P > 0.05) and 30 of 56 colon carcinoma patients (53.6%; P < 0.05) using antigen-anticor interaction methods. Comparing the frequencies of the two separate population control groups, the APC I1307K allele is associated with an estimated relative risk of 1.9 for colorectal neoplasia. Furthermore, APC I1307K carriers had greater numbers of adenomas and colorectal cancers per patient than noncarriers. The conclusion is that the APC I1307K variant leads to increased adenoma formation and colorectal cancer. The estimated relative risk for carriers may justify specific clinical screening for Turkish people expected to harbor this allele, and genetic testing in the long term may significantly promote colorectal cancer prevention in this population.

A case with a rare chromosomal abnormality: Isochromosome 18p

Case Report
Munis Dundar, Ahmet Okay Caglayan, Cetin Saatci, Korhan Arslan, Yusuf Ozkul
Genetic Counseling. 21: 69-74.

Isochromosome 18p (i(18p)), is a rare chromosomal disorder that occurs once in about every 140,000 live births and affects males and females equally. Most of the cases are due to a de novo formation but in the literature familial cases were reported. Here, we report a young female with dysmorphic features as microcephaly, frontal bossing, strabismus, low-set ears, small pinched up nose, small mouth, high palate and long philtrum, presenting a small metacentric chromosome. Besides the dysmorphic features she also has gastroesophageal reflux, spasticity, strabismus and specific brain MRI findings as dilatation of the right lateral ventricle trigonum occipital horn (colpocephaly), thinning of the corpus callosum especially of the posterior part and abnormality of the white matter myelinisation at the frontal and occipital region. Particularly the MR findings are rarely reported in the literature.

Current State of Biotechnology in Turkey

Review
Munis Dundar, Yagut Akbarova
Current Opinion in Biotechnology. 22: S3-S6.

Biotechnology is an interdisciplinary branch of science that encompasses a wide range of subjects like genetics, virology, microbiology, immunology, engineering to develop vaccines, and so on and plays a vital role in health systems, crop and seed management, yield improvement, agriculture, soil management, ecology, animal farming, cellular process, bio statistics, and so on. This article is about activities in medical and pharmaceutical biotechnology, environmental biotechnology, agricultural biotechnology and nanobiotechnology carried out in Turkey. Turkey has made some progress in biotechnology projects for research and development.

Loss of Dermatan-4-Sulfotransferase 1 Function Results in Adducted Thumb-Clubfoot Syndrome

Original Article
Munis Dundar, Thomas Mueller, Qi Zhang, Jing Pan, Beat Steinmann, Julia Vodopiutz, Robert Gruber, Tohru Sonoda, Birgit Krabichler, Gerd Utermann, Jacques U. Baenziger, Lijuan Zhang, Andreas R. Janecke
American Journal of Human Genetics. 85: 873-882.

Adducted thumb-clubfoot syndrome is an autosomal-recessive disorder characterized by typical facial appearance, wasted build, thin and translucent skin, congenital contractures of thumbs and feet, joint instability, facial clefting, and coagulopathy, as well as heart, kidney, or intestinal defects. We elucidated the molecular basis of the disease by using a SNP array-based genome-wide linkage approach that identified distinct homozygous nonsense and missense mutations in CHST14 in each of four consanguineous families with this disease. The CHST14 gene encodes N-acetylgalactosamine 4-O-sulfotransferase 1 (D4ST1), which catalyzes 4-O sulfation of N-acetylgalactosamine in the repeating iduronic acid-alpha1,3-N-acetylgalactosamine disaccharide sequence to form dermatan sulfate. Mass spectrometry of glycosaminoglycans from a patient’s fibroblasts revealed absence of dermatan sulfate and excess of chondroitin sulfate, showing that 4-O sulfation by CHST14 is essential for dermatan sulfate formation in vivo. Our results indicate that adducted thumb-clubfoot syndrome is a disorder resulting from a defect specific to dermatan sulfate biosynthesis and emphasize roles for dermatan sulfate in human development and extracellular-matrix maintenance.

Prenatally detected de novo 46, XX, t(21;21)(p12;p12) at chorionic villus sampling

Abstract
Muhammet Ensar Dogan, Fatma Colak, Asli Subasioglu Uzak, Murat Erdogan, Sevda Yesim Karabulut, Burhan Balta, Oguzhan Bahadir, Cetin Saatci, Munis Dundar
Current Opinion in Biotechnology. 22: S107-S107.

Down syndrome (trisomy 21) is one of the common intellectual disability with characteristic facies and mental retardation. This syndrome typically shows marked small ears, upslanting palpebral fissures, hypotonia, flat facial profile. In general 95% of this syndrome are resulting from non-disjunctional error of chromosome 21 during gametogenesis. 2% result from Robertsonian translocation (especially 14;21) of which 50% are familial. 2% result from mosaicism. In a retrospective study with 5737 cases, ninety five percent of them had regular trisomy 21. In 4% there was a translocation mostly Robertsonian t(14;21) and t(21;21). We report here prenatal diagnosis of a fetus with trisomy 21, 46, XX, t(21;21)(p12;p12) at chorionic villus sampling. Prenatal diagnosis was done for ultrasonography demonstrated cystic hygroma. This is a de novo translocation, parents had normal karyotypes.

Etiopathogenesis of Sheehan's Syndrome: Roles of Coagulation Factors and TNF-Alpha

Original Article
Halit Diri, Elif Funda Sener, Fahri Bayram, Nazife Tascioglu, Yasin Simsek, Munis Dundar
International Journal of Endocrinology. 12: 37.

Sheehan’s Syndrome (SS) is defined as pituitary hormone deficiency due to ischemic infarction of the pituitary gland as a result of massive postpartum uterine hemorrhage. Herein, we aimed to investigate the roles of Factor II (G20210A), Factor V (G1691A), MTHFR (C677T and A1298C), PAI-1 4G/5G, and TNF-α () gene polymorphisms in the etiopathogenesis of SS. Venous blood samples were obtained from 53 cases with SS and 43 healthy women. Standard methods were used to extract the genomic DNAs. Factor II (G20210A), Factor V (G1691A), and MTHFR (C677T and A1298C) polymorphisms were identified by real-time PCR. PAI-14G/5G and TNF-α () gene polymorphisms were detected with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. According to statistical analysis, none of the polymorphisms were found to be significantly higher in the SS group compared to the control group. Hence, we suggest that genetic factors other than Factor II, Factor V, MTHFR, PAI-1, and TNF-α gene polymorphisms should be researched in the etiopathogenesis of SS.

A case of 46, XX, t(2;17)(q37.1;q25) with recurrent miscarriage

Fatma Colak, Muhammet Ensar Dogan, Asli Subasioglu Uzak, Murat Erdogan, Sevda Yesim Karabulut, Burhan Balta, Oguzhan Bahadir, Yusuf Ozkul, Munis Dundar
Current Opinion in Biotechnology. 22: S107-S107.

Down syndrome (trisomy 21) is one of the common intellectual disability with characteristic facies and mental retardation. This syndrome typically shows marked small ears, upslanting palpebral fissures, hypotonia, flat facial profile. In general 95% of this syndrome are resulting from non-disjunctional error of chromosome 21 during gametogenesis. 2% result from Robertsonian translocation (especially 14;21) of which 50% are familial. 2% result from mosaicism. In a retrospective study with 5737 cases, ninety five percent of them had regular trisomy 21. In 4% there was a translocation mostly Robertsonian t(14;21) and t(21;21). We report here prenatal diagnosis of a fetus with trisomy 21, 46, XX, t(21;21)(p12;p12) at chorionic villus sampling. Prenatal diagnosis was done for ultrasonography demonstrated cystic hygroma. This is a de novo translocation, parents had normal karyotypes.

A family with osteogenesis imperfecta, frontonasal dysplasia, ear abnormality and mental retardation

Case Report
G. Ceylaner, S. Ceylaner, M. Dundar
Journal of Medical Genetics. 34: 527-527.

A new syndrome of microtia with unilateral renal agenesis and short stature

Case Report
Ahmet Okay Caglayan, Servi J. C. Stevens, Jozefa C. M. Albrechts, Munis Dundar, John Engelen
American Journal of Medical Genetics Part A. 158A: 1837-1840.

We report on a 13-month-old girl of first cousin parents who presented with a combination of short stature, bilateral microtia, proportionate short stature, distinctive facial features (bitemporal narrowing, long philtrum), and agenesis of the left kidney and a small right kidney. Clinical findings did not match any previously described syndromes with the anomalies seen in the patient. We performed SNP array analysis to characterize the observation as a novel syndrome and this was normal. We propose that this represents a new syndrome, likely of autosomal recessive inheritance.

Holt-Oram syndrome in two generations with translocation t(9;15)(p12;q11.2)

Case Report
10. Ahmet Okay Caglayan, Esad Koklu, Cetin Saatci, Tamer Gunes, Yusuf Ozkul, Nazmi Narin, Ali Baykan, Munis Dundar, Derya Buyukkayhan
Annals of Saudi Medicine. 28: 209-212.

A unique case of a patient with partial trisomy 22 and lipodystrophy: is it a new syndrome due to an IGF-IR mutation?

Case Report
A. O. Caglayan, J. Klammt, W. Kiess, N. Hatipoglu, R. Pfaeffle, S. Kurtoglu, C. Saatci, M. Dundar
Genetic Counseling. 21: 187-197.

A newborn male presented with intestinal malrotation, facial anomalies, hypertrichosis, hypertrophic, hyperpigmented nipples and enlarged genitals with a hyperpigmented scrotum. In addition, the patient displayed a marked lipodystrophy of trunk and limbs. His karyotype demonstrated a small supernumerary NOR-positive marker chromosome that was subsequently identified as del(22)(q12->qter). This extra structurally abnormal chromosome probably derives from a maternal balanced translocation, which was found by karyotype analysis of the mother. The patient’s growth hormone (GH) serum levels were elevated, whereas serum insulin-like growth factor 1 (IGF-I) was almost undetectable. Molecular genetic analysis of the IGF-I and type 1 IGF receptor (IGF-IR) genes revealed a heterozygous mutation within exon 21 of the IGF-IR (Pro1257Ser). Findings in our patient correlate to a large extent with partial trisomy 22. Phenotypic variation from classical partial trisomy 22 syndrome may lie within the variability of this syndrome, originate from disturbances within the GH-IGF/IGF-IR axis or, alternatively, reflect the pathogenesis of a new syndrome due to the synergistical impact of the combination of the genetic aberrations. Additional studies are necessary to confirm or refute this hypothesis.

Lack of association between the Glu298Asp polymorphism of endothelial nitric oxide synthase and slow coronary flow in the Turkish population

Case Report
Ahmet Okay Caglayan, Nihat Kalay, Cetin Saatci, Arif Yalcin, Hilal Akalin, Munis Dundar
Canadian Journal of Cardiology. 25: E69-E72.

BACKGROUND: Coronary endothelial dysfunction plays an important pathogenetic role in patients with slow coronary flow (SCF). No data exist regarding the possible contribution of the Glu298Asp polymorphism genotype of the endothelial nitric oxide synthase (eNOS) gene to human SCF in the literature.

OBJECTIVE: To investigate the association between SCF and the Glu298Asp polymorphism of the eNOS gene.

METHODS: The study population consisted of 85 consecutive patients. The patient group included 66 patients with angiographically proven normal coronary arteries with SCF, and 19 subjects with normal coronary arteries with no SCF. The thrombolysis in myocardial infarction frame count was used for the diagnosis of SCF. The Glu298Asp polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism.

RESULTS: The baseline characteristics were similar between the two groups, except for high-density lipoprotein cholesterol, which was higher in the SCF group than in the controls. The genotype distribution of Glu298Asp was as follows: GG 26%, GT 56% and TT 12%, where G is guanine and T is thymine. There was no difference in the frequency of the various genotypes or the alleles in patients with SCF versus normal controls.

CONCLUSIONS: The Glu298Asp polymorphism genotype of the eNOS gene is not a risk factor for SCF in the present study population.

Inherited diseases and syndromes leading to aortic aneurysms and dissectionsGenes affect virtually all human characteristics and diseases. These influences can be ascertained in individual patients through a review of the family history, physical examination and the use of medical diagnostics. Aneurysms and dissections are a leading cause of morbidity and mortality, in addition to medical expense, and, on the whole, their specific molecular mechanisms are beginning to be identified. Over the past decade, genetic tests have become available for numerous heritable disorders especially inherited with mendelian models. An important fact is that the results of genetic tests may also be useful beyond the individual affected by the genetic disorder. Depending upon the disorder, knowledge of carrier status may be important. Because of these facts, some essential information regarding basic genetics of aneurysm and dissection has been presented in this study.

Original Article
A. O. Caglayan, M. Dundar
Eur J Cardiothorac Surg. 35: 931-40.

Genes affect virtually all human characteristics and diseases. These influences can be ascertained in individual patients through a review of the family history, physical examination and the use of medical diagnostics. Aneurysms and dissections are a leading cause of morbidity and mortality, in addition to medical expense, and, on the whole, their specific molecular mechanisms are beginning to be identified. Over the past decade, genetic tests have become available for numerous heritable disorders especially inherited with mendelian models. An important fact is that the results of genetic tests may also be useful beyond the individual affected by the genetic disorder. Depending upon the disorder, knowledge of carrier status may be important. Because of these facts, some essential information regarding basic genetics of aneurysm and dissection has been presented in this study.

Biotechnology worldwide and the 'European Biotechnology Thematic Network' Association (EBTNA)

Review
F. Bruschi, M. Dundar, P. B. Gahan, K. Gartland, M. Szente, M. P. Viola-Magni, Y. Akbarova
Curr Opin Biotechnol. 22 Suppl 1: S7-14.

The European Biotechnology Congress 2011 held under the auspices of the European Biotechnology Thematic Network Association (EBTNA) in conjunction with the Turkish Medical Genetics Association brings together a broad spectrum of biotechnologists from around the world. The subsequent abstracts indicate the manner in which biotechnology has permeated all aspects of research from the basic sciences through to small and medium enterprises and major industries. The brief statements before the presentation of the abstracts aim to introduce not only Biotechnology in general and its importance around the world, but also the European Biotechnology Thematic Network Association and its aims especially within the framework of education and ethics in biotechnology.

Sacrococcygeal teratoma in a fetus with prenatally diagnosed partial trisomy 10q (10q24.3-->qter) and partial monosomy 17p (p13.3-->pter)

Case Report
C. Batukan, M. T. Ozgun, M. Basbug, O. Caglayan, M. Dundar, N. MuratOBJECTIVE: Clinical features of the distal 10q trisomy syndrome consist of mental retardation, facial dysmorphism and renal and cardiac anomalies. The presence of a sacrococcygeal teratoma (SCT) in a fetus with distal 10q trisomy has not been reported yet. METHODS: A 33-year-old, G5, P2 woman with a singleton pregnancy was referred to our clinic at 24 weeks of gestation for further evaluation of a fetal sacral exophytic mass. Detailed fetal sonographic examination together with chromosomal analysis by amniocentesis was performed. RESULTS: The scan revealed a large SCT together with a persistent right umbilical vein, cardiomegaly, bilateral mild hydronephrosis and intrauterine growth retardation. The fetal karyotype showed distal 10q trisomy (10q24.3-->qter) distal monosomy 17 (p13-->pter). The fetus died after a preterm delivery at 28 weeks of gestation. Postnatal examination confirmed the prenatal findings and added the typical facial features of this syndrome, which consisted of prominent forehead, small nose with depressed nasal bridge, micrognathia and bow-shaped mouth. CONCLUSION: This case provides further evidence of a possible association between chromosomal aberrations in SCTs.
Prenat Diagn. 27: 365-8.

OBJECTIVE: Clinical features of the distal 10q trisomy syndrome consist of mental retardation, facial dysmorphism and renal and cardiac anomalies. The presence of a sacrococcygeal teratoma (SCT) in a fetus with distal 10q trisomy has not been reported yet.

METHODS: A 33-year-old, G5, P2 woman with a singleton pregnancy was referred to our clinic at 24 weeks of gestation for further evaluation of a fetal sacral exophytic mass. Detailed fetal sonographic examination together with chromosomal analysis by amniocentesis was performed.

RESULTS: The scan revealed a large SCT together with a persistent right umbilical vein, cardiomegaly, bilateral mild hydronephrosis and intrauterine growth retardation. The fetal karyotype showed distal 10q trisomy (10q24.3–>qter) distal monosomy 17 (p13–>pter). The fetus died after a preterm delivery at 28 weeks of gestation. Postnatal examination confirmed the prenatal findings and added the typical facial features of this syndrome, which consisted of prominent forehead, small nose with depressed nasal bridge, micrognathia and bow-shaped mouth.

CONCLUSION: This case provides further evidence of a possible association between chromosomal aberrations in SCTs.

Associated anomalies in asymmetric crying facies and 22q11 deletion

Case Report
M. Akcakus, Y. Ozkul, T. Gunes, S. Kurtoglu, N. Cetin, A. R. Kisaarslan, M. Dundar
Genetic Counseling. 14: 325-330.

Congenital asymmetric crying facies, a minor congenital anomaly due to unilateral absence or hypoplasia of the depressor anguli oris muscle, is associated at times with major congenital anomalies. A large number of asymmetric crying facies cases with chromosome 22q11 microdeletions have presently been reported. Fluorescence in situ hybridization (FISH) analysis for 22q11 deletion was performed on 8 infants with asymmetric crying facies. Five of our patients had at least one associated systemic anomaly. Two of 5 patients had conotruncal heart disease (Cayler cardiofacial syndrome). In three of the affected infants, we failed to reveal additional congenital malformation. The 22q11 deletion was present in only one patient. This baby had congenital hypoparathyroidism, severe neonatal hypocalcaemia and tetralogy of Fallot. We suggest, a 22q11 deletion should be excluded not in all cases but in cases with Cayler cardiofacial syndrome and in ACF associated with additional congenital anomalies.

Analysing the role of MDM2 SNP309 in patients with glioblastoma multiforme

Abstract
Yagut Akbarova, Munis Dundar, Hilal Akalin, Dicle Aslan, Ozlem Canoz, Yasin Ada, Oguz Yildiz.
Current Opinion in Biotechnology. 24: S98-S98.

The single nucleotide polymorphism SNP309 with a change from T to G in the promoter region of the MDM2 gene is shown to increase the MDM2 protein levels and attenuates the p53 levels and associates with disease progression in several tumours. In this study, the role of the MDM2 SNP309 T>G polymorphism was investigated with regard to the clinical outcome in glioblastoma multiform patients. Genomic DNA was isolated from paraffin-embedded brain tissue samples of 115 patients diagnosed with GBM, some of whom were treated with radiation therapy + temozolomide and the others were treated with only radiation therapy. The MDM2 SNP309 genotype was amplified by PCR, in which two distinct primer pairs were used for each of the alleles. Investigation of genomic DNA of the 115 GBM patients found that 11 (10%) of them were homozygous for TT, 77 (67%) of them were heterozygous for TG, and 27 (23%) of them were homozygous for GG. There was a statistically significant difference between glioblastoma patients and healthy subjects with respect to the distribution of SNP309 genotype (P = 0.03, chi-square test). Our results suggest that in GBM patients MDM2 SNP309 polymorphism homozygote GG and heterozygote TG were significantly associated with increased tumour risk.

An autosomal recessive adducted thumb-club foot syndrome observed in Turkish cousins

Case Report
Dundar M, Demiryilmaz F, Demiryilmaz I, Kumandas S, Erkilic K, Kendirci M, Tuncel M, Ozyazgan I, Tolmie JL.
Clinical genetics, 51(1): 61-4.

Male and female cousins, the offspring of consanguineous Turkish parents, have been affected by a hitherto unreported combination of problems comprising moderate to severe psychomotor developmental delay, ocular anterior chamber abnormality, facial dysmorphisms (broad, bossed forehead, late-closing fontanelle, telecanthus, downslanting palpebral fissures, posteriorly rotated ears, downturned angles of mouth), arachnodactyly and distal arthrogryposis with severely adducted thumbs and club feet. This striking phenotype has some similarities with the multiple pterygium syndrome (Escobar syndrome), but it most likely represents a distinct condition caused by an autosomal recessive gene defect.