Gebeliklerde düşük östriyol düzeyleri nasıl yönetilir, tek merkez deneyimi

Objective: Low estriol (uE3) levels in the second-trimester screening for Down syndrome may be the result of fetal demise, congenital abnormalities, or some genetic hormonal disorders of the fetus. Although X-linked ichthyosis, a microdeletion syndrome with mild ichthyosis, which causes steroid sulfatase (STS) deficiency, is the most common genetic cause, second-trimester screening tests calculate the risk for a less common and severe disorder known as the Smith Lemli Opitz syndrome (SLOS). We aimed to investigate the outcomes of pregnancies with low uE3 levels in Down syndrome screening and emphasize the high prevalence of STS deficiency instead of SLOS in such cases. Methods: Fifteen pregnancies with very low uE3 levels and high risk for trisomy and/or SLOS in screening tests were evaluated and tested for STS deficiency and SLOS. Results: Seven of the pregnancies had STS microdeletion syndrome, while additional two cases were supposed to have STS gene mutation according to family and/or postnatal history. Although one fetal death was recorded, no chromosomal abnormality, SLOS, or congenital malformation was recorded in our series. Conclusions: SLOS is a very severe and rare syndrome. The risk estimation for SLOS in screening tests causes stress for pregnant women and healthcare givers. We recommend the addition of risk estimation for STS deficiency when a low uE3 level is detected in the screening test.Amaç: İkinci trimester Down sendromu tarama testlerindeki düşük östriyol (uE3) seviyesi, fetal ölüm, konjenital anormallikler veya fetüsün çeşitli genetik hormonal bozukluklarından kaynaklanabilir. Steroid sülfataz (STS) eksikliğine neden olan ve hafif iktiyozla seyreden bir mikrodelesyon sendromu olan X’e bağlı iktiyoz en yaygın genetik neden olmasına rağmen, ikinci trimester tarama testleri daha az yaygın ve daha şiddetli bir hastalık olan Smith Lemli Opitz Sendromu (SLOS) için risk hesaplamaktadır. Down sendromu taramasında uE3 düzeyi düşük olan gebeliklerin sonuçlarını araştırmayı ve bu gibi durumlarda SLOS yerine STS eksikliğinin yüksek prevalansını vurgulamayı amaçladık. Yöntemler: Tarama testlerinde uE3 seviyeleri çok düşük olan ve trizomi ve/veya SLOS açısından yüksek risk taşıyan on beş gebelik STS eksikliği ve SLOS açısından değerlendirilmiş ve test edilmiştir. Bulgular: Gebeliklerin yedisinde STS mikrodelesyon sendromu bulunurken, ek iki olguda aile ve/veya doğum sonrası öyküye dayanarak STS gen mutasyonu düşünüldü. Bir fetal ölüm tespit edildi. Ek kromozom anomalisi, SLOS veya konjenital malformasyon tespit edilmedi. Sonuçlar: SLOS çok ağır seyreden ve nadir görülen bir sendromdur. Tarama testlerinde SLOS için risk tahmini hamileler ve sağlık çalışanları için strese neden olmaktadır. Anksiyeteyi önlemek için tarama testlerinde düşük bir uE3 seviyesi tespit edildiğinde STS eksikliği için risk tahmininin eklenmesini öneririz

Effects of chromosomal translocations on sperm count in azoospermic and oligospermic cases

Purpose: A number of mechanisms have been proposed for the effect of chromosomal translocations on spermatogenesis and sperm maturation. However, there are still numerous ambiguous issues regarding these two processes. The aim of this study is to evaluate the effect of chromosome break areas on sperm count in the light of the literature. Material and Methods: The study was conducted on the data of 16 male patients with reciprocal or Robertsonian translocation among 152 patients who were admitted to Adana Numune Training and Research Hospital and Kanuni Sultan Suleyman Training and Research Hospital Genetic Diagnosis Centers between 2013 and 2016 due to azoospermia and oligospermia. Results: 11 of these patients had reciprocal and five patients had Robertsonian translocations. All the patients with Robertsonian translocations were detected with azoospermia. Of the patients with reciprocal translocation, five of them were azoospermic and six of them were severe oligospermic. Conclusion: A total of 21 chromosomal breakpoints were identified in the 11 patients with reciprocal translocations. These chromosomal breakpoints may contribute to the clarification of ambiguous issues related to spermatogenesis and sperm maturation. The results also showed the importance of genetic counselling in patients with translocations

Does fetal MR alter the management of pregnancy in the diagnosis of isolated corpus callosum agenesis?

Objective To determine if fetal MR alters the management of pregnancy and family decisions in the isolated corpus callosum agenesis (CCA) cases or not. Methods Fetal MR was carried out in the cases diagnosed with CCA in the Perinatology Unit of our hospital between 2013 and 2019 after they were differentiated as complex and isolated CCA cases. The impact of MR results on the family decisions and their approaches towards termination were assessed. Results A total of 109 out 139 cases were evaluated as isolated CCA. While 93 (85.32%) of them were diagnosed with the complete CCA, 16 (14.68%) cases were diagnosed with the partial CCA. When the period after 2017 during which fetal MR was recommended to all patients was reviewed, it was seen that 7 (23.3%) of 30 cases who underwent fetal MR and 2 (20%) of 10 cases who did not undergo fetal MR terminated their pregnancies. There was no statistical difference between two groups in terms of the decisions of the patients for gestational termination who did and did not undergo fetal MR. Conclusion Fetal MR imaging in the isolated CCA does not change the decisions of the families for the gestational termination. In terms of the termination decision, week of gestation and socio-cultural factors may have more impacts

Loss-of-Function Variants in EFEMP1 Cause a Recognizable Connective Tissue Disorder Characterized by Cutis Laxa and Multiple Herniations

Hereditary disorders of connective tissue (HDCT) compromise a heterogeneous group of diseases caused by pathogenic variants in genes encoding different components of the extracellular matrix and characterized by pleiotropic manifestations, mainly affecting the cutaneous, cardiovascular, and musculoskeletal systems. We report the case of a 9-year-old boy with a discernible connective tissue disorder characterized by cutis laxa (CL) and multiple herniations and caused by biallelic loss-of-function variants in EFEMP1. Hence, we identified EFEMP1 as a novel disease-causing gene in the CL spectrum, differentiating it from other HDCT.</jats:p

Phenotypic expansion in DDX3X - a common cause of intellectual disability in females

De novo variants in DDX3X account for 1-3% of unexplained intellectual disability (ID) cases and are amongst the most common causes of ID especially in females. Forty-seven patients (44 females, 3 males) have been described. We identified 31 additional individuals carrying 29 unique DDX3X variants, including 30 postnatal individuals with complex clinical presentations of developmental delay or ID, and one fetus with abnormal ultrasound findings. Rare or novel phenotypes observed include respiratory problems, congenital heart disease, skeletal muscle mitochondrial DNA depletion, and late-onset neurologic decline. Our findings expand the spectrum of DNA variants and phenotypes associated with DDX3X disorders

Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Report of a family with craniofrontonasal syndrome

Craniofrontonasal syndrome (CFNS, OMIM 304110) paradoxically presents a severe phenotype in heterozygous females and a mild or a normal phenotype in hemizygous males. Hypertelorism is seen in almost all of the female CFNS patients; craniosynostosis, facial asymmetry, and bifid nose are the other major clinical features. Most of the males are mildly affected, frequently only with hypertelorism. Here, we report a family with a G151S mutation in the EFNB1 gene. The mutation was identified in two severely affected sisters and paradoxically in their clinically unaffected father. The father on whom we report is the first male patient genetically proved to carry a CFNS-causing mutation and not presenting any signs nor symptoms of CFNS. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved

Evaluation of both chromosome analysis and thrombophilia parameters of 306 couples studying for recurrent pregnancy loss: a single center experience

Bu çalışmanın amacı, hastanemize tekrarlayan gebelik kaybı nedeniyle başvuran çiftlere uygun genetik danışmanlık verebilmek için hem majör kromozom anomalilerinin hem de trombofili parametrelerinin etiyolojideki rolünü araştırmaktır. Gereç ve Yöntemler: Çalışmamıza tekrarlayan gebelik kaybı nedeniyle Başakşehir Çam ve Sakura Şehir Hastanesi Genetik Hastalıklar Değerlendirme Merkezi'ne başvuran toplam 306 çift dâhil edildi. Tüm hastalarda kromozom analizleri ve 306 bayanda trombofili parametrelerinin analizleri gerçekleştirildi. Bulgular: Çalışmamızda toplam 306 çiftin 13’ünde (%4,25) polimorfizm dışında kalan kromozomal anomaliler tespit edildi. 4 hastada robertsonian translokasyon, 3 hastada resiprokal traslokasyon, 4 hastada mozaik kromozom kuruluşu, 1 hastada yapısal kromozal dengesizlik (derivatif kromozom) ve 1 hastada sayısal kromozal anomali varlığı tespit edilmiştir. Geriye kalan 293 çiftin kromozom analizi normaldi. Çalışmamızda trombofili parametreleri analiz edilen 306 bayan olgunun yaklaşık %10’unda Faktör V Leiden varyantı saptanırken, Faktör II G20210A varyantı ise yaklaşık %3,5 oranında saptanmıştır. 3 hastada (%1) Faktör V Leiden varyantı homozigot, 27 hastada ise Faktör V Leiden varyantı (%8,8) heterozigot olarak saptanmıştır. 10 hastanın (%3,3) Faktör II G20210A varyantını heterozigot olarak taşıdıkları saptanmıştır. Faktör II G20210A varyantını homozigot olarak taşıtan bir hasta çalışmamızda saptanmamıştır. Sonuç: Mevcut bilgiler ve geçmişteki literatür çalışmaları eşliğinde tekrarlayan gebelik kaybı nedeniyle değerlendirilen çiftlerde etiyolojiyi aydınlatmak için kromozom analizi ve trombofili parametrelerinin değerlendirilmesini ve bu parametrelerde ilişkili olduğu düşünülen bir neden saptandığında tedavi imkanları bulunduğundan dolayı özellikle yardımcı üreme tekniklerinden önce bu analizlerin yapılmasını önermekteyiz.The aim of this study is to investigate the role of both major chromosomal anomalies and thrombophilia parameters in the etiology, in order to provide appropriate genetic counseling to couples who applied to our hospital due to recurrent pregnancy loss. Material and Methods: A total of 306 couples who applied to Başakşehir Çam and Sakura City Hospital Genetic Diagnosis Center due to recurrent pregnancy loss were included in our study. Chromosome analyzes were performed in all patients and analyzes of thrombophilia parameters were done in 306 women. Results: In our study, chromosomal anomalies other than polymorphism were detected in 13 (4.25%) of a total of 306 couples. Robertsonian translocation in 4 patients, reciprocal translocation in 3 patients, mosaic chromosome in 4 patients, structural chromosomal imbalance (derivative chromosome) in 1 patient and numerical chromosomal anomaly in 1 patient were detected. In our study, Factor V Leiden variant was detected in approximately 10% of 306 female cases whose thrombophilia parameters were analyzed, while Factor II G20210A was detected in 3.5%. Leiden variant was found to be homozygous in 3 patients (1%) and heterozygous in 27 patients (8.8%), while 10 patients (3.3%) were heterozygous for the G20210A variant. Conclusion: In the light of current information, we recommend that chromosomal analysis and thrombophilia parameters be evaluated in order to clarify the etiology in couples who are evaluated for recurrent pregnancy loss especially before assisted reproductive techniques since there are treatment possibilities when a cause thought to be related to these parameters