CLINICAL AND MOLECULAR RESULTS OF SIX CASES WITH ROBERTS SYNDROME: REVIEW OF CASES FROM TURKIYE

Öz

Objective: Roberts syndrome is a rare autosomal recessive disease characterized by limb defects, prenatal onset growth retardation, and craniofacial anomalies. We aimed to compare the clinical and molecular findings of six cases with Roberts syndrome with the previously reported patients from Turkiye and to emphasize that the definitive diagnosis can be made in the intrauterine period with cytogenetic tests in the early period without the need to wait for molecular test results. Materials and Methods: Six cases, diagnosed with Roberts syndrome, in our outpatient clinic of Istanbul University, Istanbul Medical Faculty, Medical Genetics Department between 2015-2021 were included in the study. The family history, clinical information, and cytogenetic and molecular findings of the patients were retrospectively reviewed and compared with cases reported from Turkiye in the literature. G and C-banding techniques and Sanger sequencing of the ESCO2 gene were performed. Results:Pathogenic variants in homozygous in four and compound heterozygous in two patients in the ESCO2 gene were identified. Compound heterozygous c.[417dup];[1131+1G>A] (p.[(Pro140Thrfs*8)];[(?)]) in case 1, and c.[1111dup];[760del] (p.[(Thr371Asnfs*32)];[(Thr254Leufs*13)]) in case 6, homozygous c.1131+1G>A (p.(?)) in case 2, case 3 and case 5, and homozygous c.1111dup (p.(Thr371Asnfs*32)) mutations in case 4 were detected. The variants reported in our case series were previously associated with the disease. The first demonstration of the c.760del mutation in a Turkish case contributed to the mutation profile in our population that caused this disease. Although all previously reported Turkish patients were homozygous, we have detected two patients with compound heterozygous mutations indicating that the disease should also be considered in families with no consanguinity.

Anahtar Kelimeler

• ESCO2
• Roberts Syndrome
• tetraphocomelia

ROBERTS SENDROMLU ALTI OLGUNUN KLİNİK VE MOLEKÜLER SONUÇLARI İLE TÜRKİYE'DEN BİLDİRİLEN OLGULARIN GÖZDEN GEÇİRİLMESİ

Öz

Amaç: Roberts sendromu; ekstremite anomalileri, prenatal başlangıçlı büyüme gelişme geriliği ve kraniyofasiyal anomaliler ile karakterize nadir görülen otozomal resesif kalıtılan bir hastalıktır. Roberts sendromlu altı olgunun klinik ve moleküler bulgularını Türkiye'den daha önce bildirilen olgularla karşılaştırmayı ve moleküler test sonuçlarını beklemeye gerek kalmadan erken dönemde sitogenetik testlerle kesin tanının intrauterin dönemde yapılabileceğini vurgulamayı amaçladık. Gereç ve Yöntem: 2015-2021 yılları arasında İstanbul Üniversitesi İstanbul Tıp Fakültesi Tıbbi Genetik Anabilim Dalı polikliniğimizde Roberts sendromu tanısı alan altı olgu çalışmaya dahil edildi. Hastaların aile öyküsü, klinik bilgileri, sitogenetik ve moleküler bulguları retrospektif olarak incelendi ve literatürde Türkiye'den bildirilen olgularla karşılaştırıldı. G ve C-bantlama teknikleri ve ESCO2 geninin Sanger dizilimi gerçekleştirildi. Bulgular:ESCO2 geninde dört olguda homozigot ve iki olguda bileşik heterozigot patojenik varyantlar tespit edildi. Olgu 1’de birleşik heterozigot c.[417dup];[1131+1G>A] (p.[(Pro140Thrfs*8)];[(?)]) ve olgu 6’da c.[1111dup];[760del](p.[(Thr371Asnfs*32)]; [(Thr254Leufs*13)]) ile olgu 2, olgu 3 ve olgu 5’te homozigot c.1131+1G>A (p.(?)), olgu 4’te homozigot c.1111dup (p.(Thr371Asnfs*32)) mutasyonları saptandı. Olgu serimizde bildirilen patolojik varyantlar daha önce hastalıkla ilişkilendirilmiştir. c.760del mutasyonunun ilk kez Türk bir olguda gösterilmesi bu hastalığa neden olan toplumuzdaki mutasyon profiline katkısı olmuştur. Ayrıca literatürde daha önce yayınlanan Türk olgularda homozigot mutasyon saptanmasına rağmen bizim olgu serimizde ebeveynleri arasında akrabalık ilişkisi olmayan iki olguda birleşik heterozigot mutasyonun gösterilmesi bu sendromun akrabalık ilişkisi olmayan vakalarda da rastlanılacağını göstermektedir.

Anahtar Kelimeler

• ESCO2
• Roberts sendromu
• tetrafokomeli

Kaynakça

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