Amaç: Holoprosensefali (HPE), ön beyin orta hat bölünmesinde en sık görülen gelişimsel bozukluktur. Etiyolojisinde, çevresel, genetik ve multi faktöriyel hastalıklar rol oynamaktadır. Vakaların yaklaşık yarısında, trizomi 13 başta olmak üzere, trizomi 18 ve triploidi gibi sayısal anomaliler ve yapısal kromozom anomalileri bulunmaktadır. Olguların ~%25'inde tek gen mutasyonları gösterilmiştir. Bu retrospektif çalışmada fetal dönemde saptanan 127 fetüste HPE etiyolojisinde rol oynayan faktörleri araştırmayı amaçladık. Gereç ve Yöntem: Bu çalışma, 25 yıllık bir periyotta fetal ultrasonografide HPE tanısı konmuş 127 fetusta yapılan klasik karyotipleme, floresan in situ hibridizasyon (FISH) ve aCGH incelemelerinin sonuçlarını içermektedir. Bulgular: Bu kohortta olguların 64 (%50,39)’ünde bir kromozom anomalisi tespit edildi. En sık görülen sayısal kromozomal anomali beklendiği gibi trizomi 13 (n=38) idi , bunu sırasıyla trizomi 18 (n=8) ve triploidi (n=5) izlemiştir. Yapısal kromozom anomalilerinden terminal 7q delesyonu en sık görülen anomaliydi (n=10, 5’i de novo, 4’ü maternal translokasyonun dengesiz ürünü, 1 olgunun kökeni ise bilinmiyordu). Bir olguda 18. kromozomun p kolunda bir delesyon saptandı. Kalan 2 olguda tesadüfi olarak trizomi 20 ve 11. kromozomda perisenttrik bir inversiyon saptandı. Sonuç: Bu çalışma, HPE klinik bulguların varlığında sitogenetik ve moleküler sitogenetik çalışmaların birlikte veya tamamlayıcı olarak yapılması gerektiğini göstermektedir. Özellikle aCGH çalışması submikroskopik yapısal kromozomal anomalilerin boyutlarını ve kırık noktalarını, bölgede yer alan genleri belirlemekte olduğu kadar HPE etiyolojisinde rol oynayabilecek olası yeni genleri tanımlamak için de yapılmalıdır.
Objective To discuss the prenatal diagnosis, obstetrical management, and perinatal outcome of duodenal atresia, and investigate the incidence of associated malformations and chromosomal anomalies. Materials and methods The data about 27 fetuses with duodenal atresia which were diagnosed on prenatal sonographic evaluation, and confirmed postnatally, among 20401 high risk pregnancies who were referred to Prenatal Diagnosis Unit of Obstetrics and Gynecology Department of Istanbul Medical Faculty between 1988 and 1999, are analyzed. Presence of polihydramnios, gestational week at diagnosis, associated malformations and chromosomal abnormalities, and perinatal outcomes were evaluated. Fisher's exact test is used for statistical analysis. Results Duodenal atresia was diagnosed in 43 fetuses, but postnatal outcomes of 38 fetuses could be obtained. Ten of the fetuses had additional abnormalities in 27 cases whom diagnosis was confirmed. Nine chromosomal abnormalities (33.3%) including seven trisomy 21 (29.6%), one deletion, one translocation anomaly detected. The perinatal mortality of duodenal atresia is found 44.4% with 12 pre and postnatal deaths. Fifteen infants discharged in a healthy condition after operations. Conclusion Duodenal atresia, especially in the presence of associated abnormalities has a high perinatal mortality. Establishment of diagnosis in prenatal period, even in the late stages of gestation, may contribute the obstetrical and neonatal management.
Azoospermia can be diagnosed with spermiogram analysis, and karyotyping is the golden standard to explain the etiology. In this study, we investigated two male cases with azoospermia and male infertility for chromosomal abnormalities. Their phenotypes and physical and hormonal examinations were both normal. In karyotyping G-banding and NOR staining, a rare ring chromosome 21 abnormality was detected in the cases and no microdeletion in chromosome Y. Ring abnormality, deletion size, and deleted regions were shown with subtelomeric FISH (.ish r(21)(p13q22.3?)(D21S1446-)) and array CGH analyses. Due to the findings, bioinformatics, protein, and pathway analyses were done to detect a candidate gene through common genes in two cases' deleted regions or ring chromosome 21.
Abstract Carriers of apparently balanced chromosomal rearrangements (ABCRs) have a 2-3-fold higher risk of carrying an abnormal phenotype, when compared to the average population. Apparently balanced chromosomal rearrangements can be imbalanced at the submicroscopic level, and changes in the gene structure, formation of a new chimeric gene, gain or loss of function of the genes and altered imprinting pattern may also affect the phenotype. Chromosomal microarray (CMA) is an efficient tool to detect submicroscopic imbalances at the breakpoints as well as in the whole genome. We aimed to determine the effectiveness of array-comparative genomic hybridization (aCGH) application in phenotypically affected cases with ABCRs at a single center from Turkey. Thirty-four affected cases (13 prenatal, 21 postnatal) carrying ABCRs were investigated with CMA. In postnatal series, ABCRs were familial in 7 and de novo in 14 cases. Seven de novo cases were imbalanced (in postnatal series 33.3% and in de novo cases 50.0%). Out of 13 prenatal cases, five were familial and eight were de novo in origin and two de novo cases were imbalanced (in 15.4% prenatal series and in 25.0% de novo cases). No cryptic imbalance was observed in familial cases. The anomaly rates with array studies ranged between 14.3-25.0% in familial and between 20.0-57.5% in de novo cases of postnatal series in the literature. Studies focused on prenatal ABCR cases with abnormal ultrasound findings are limited and no submicroscopic imbalance was reported in the cohorts. When de novo postnatal or prenatal results were combined, the percentage of abnormalities detected by CMA was 40.9%. Taking this contribution into consideration, all ABCRs should be investigated by CMA even if the fetal ultrasound findings are normal.
In two large Turkish consanguineous families, a locus for autosomal recessive nonsyndromic hearing loss (ARNSHL) was mapped to chromosome 6p21.3 by genome-wide linkage analysis in an interval overlapping with the loci DFNB53 (COL11A2), DFNB66, and DFNB67. Fine mapping excluded DFNB53 and subsequently homozygous mutations were identified in the lipoma HMGIC fusion partner-like 5 (LHFPL5) gene, also named tetraspan membrane protein of hair cell stereocilia (TMHS) gene, which was recently shown to be mutated in the "hurry scurry" mouse and in two DFNB67-linked families from Pakistan. In one family, we found a homozygous one-base pair deletion, c.649delG (p.Glu216ArgfsX26) and in the other family we identified a homozygous transition c.494C>T (p.Thr165Met). Further screening of index patients from 96 Turkish ARNSHL families and 90 Dutch ARNSHL patients identified one additional Turkish family carrying the c.649delG mutation. Haplotype analysis revealed that the c.649delG mutation was located on a common haplotype in both families. Mutation screening of the LHFPL5 homologs LHFPL3 and LHFPL4 did not reveal any disease causing mutation. Our findings indicate that LHFPL5 is essential for normal function of the human cochlea.
Wolf-Hirschhorn syndrome is caused by distal deletion of the short arm of chromosome 4 (4p-). We report a case in which intrauterine growth restriction, hypospadias and foot deformity were detected by prenatal ultrasound examination at 29 weeks of gestation. A 31-year-old gravida 2 partus 1 woman was referred at 29 weeks' gestation with suspicion of intrauterine growth restriction. Sonographic examination revealed deformity of the right lower limb and undescended testes with an irregular distal penis. A cordocentesis was performed and chromosome analysis revealed a 46,XY,del(4)(p14) karyotype. The prenatal detection of intrauterine growth restriction, hypospadias and foot deformity should lead doctors to suspect the presence of Wolf-Hirschhorn syndrome.
