부산대학교 도서관

INTRODUCTION One of the most prevalent autosomal recessive disorders in Caucasians is cystic fibrosis (CF). The condition is marked by progressive lung damage brought on by chronic infection, pancreatic exocrine [...]
Objective: In a multiethnic community, our goal was to assess the applicability of this method. Here we offer a collection of 112 diagnostic prenatal samples for which a comprehensive study of exons, exons/intron boundaries, and major rearrangements has been investigated in prenatal samples of fetuses with suspected cystic fibrosis over the past decade. Methods: For the CFTR mutation study, 112 prenatal samples (amniotic fluid, chorionic villi, or cultured cells from amniotic fluid or chorionic villi) were brought into our lab. QIAseq Targeted NGS DNA Panel (Qiagen, Hilden, Germany) was performed to analyze the CFTR gene (27 exons). Results: The pathogenic variation NM000492.4(CFTR):c.3454G>C was the most often found (p.Asp1152His), which accounted for 50% of the classic pathogenic CF variants in the study population. Compound heterozygous CFTR pathogenic variations were detected in one of our patients. NM000492.3(CFTR):c.2620-15C>G and NM000492.3(CFTR):c.2756A>G Two variants, one of which was reported as VUS and the other as pathogenic, were detected in a 17-week-old fetus (0.89%). Fetus inherited the NM000492.3(CFTR):c.2756A>G variant from mother and the NM000492.3(CFTR):c.2620-15C>G variant from father. There is an isolated hyperechoic bowel sign at 17 weeks of pregnancy. Conclusion: In our case series, genetic analyzes suggest that an affected child may be heterozygous for CFTR mutations, compound heterozygous for two clinically significant recessive mutations inherited from healthy carrier parents. Early prenatal genetic testing pretesting and posttesting genetic counseling is crucial in the management of future pregnancies in heterozygous couples which are healthy carriers for CFTR mutations. Keywords: Cystic fibrosis, genetic testing, CFTR mutations Amac: Cok irkli bir populasyonda kistik firozun prenatal donemde genetik acidan analizini ve sonuc olarak varyant sikligini belirlemeyi amacladik. Son on yilda kistik firozdan suphelenilen fetuslerin dogum oncesi orneklerinden ekzonlar, ekzonlar/intron sinirlari ve yeniden duzenlemeler hakkinda kapsamli bir calismanin arastirildigi 112 dogum oncesi tani orneginden olusan bir hasta populasyon verisini sunuyoruz. Gerec ve Yontem: CFTR mutasyon analizi icin 112 prenatal ornegin (amniyotik sivi, koryonik villus veya amniyotik sivi veya koryonik villustan kulture edilmis hucrelerin) laboratuvarimizda analizleri yapildi. CFTR genini (27 ekzon) analiz etmek icin QIAseq Hedefl NGS DNA Paneli (Qiagen, Hilden, Almanya) kullanilmistir. Bulgular: En yaygin olarak tanimlanan patojenik varyantimiz, calisma populasyonundaki klasik patojenik varyantlarin %50'sini olusturan NM000492.4(CFTR):c.3454G>C (p.Asp1152His) idi. Hastalarimizdan birinde bilesik heterozigot CFTR patojenik varyasyonu tespit edildi. NM000492.3(CFTR):c.2620-15C>G ve NM000492.3(CFTR):c.2756A>G olmak uzere, 17 haftalik fetuste sirayla ilki VUS digeri patojenik olarak bildirilen iki varyant tespit edildi (%0,89). Fetus, NM000492.3(CFTR):c.2756A>G varyantini anneden ve NM000492.3(CFTR):c.2620-15C>G varyantini babadan kalitim olarak almistir. Gebeligin 17. haftasinda izole hiperekojen bagirsak bulgusu mevcuttur. Sonuc: Bizim olgu serimizde, genetik analizler, etkilenen bir cocugun CFTR mutasyonlari icin heterozigot olabilecegini, saglikli tasiyici ebeveynlerden kalitilan klinik olarak anlamli iki resesif mutasyon icin bilesik heterozigot olabilecegini dusundurmektedir. Erken dogum oncesi genetik testler, on test ve test sonrasi genetik danismanlik, CFTR mutasyonlari icin saglikli tasiyicilar olan heterozigot bir ciftte gelecekteki gebeliklerin yonetiminde cok onemlidir. Anahtar Kelimeler: Kistik firozis, genetik test, CFTR mutasyonlari