PKHD1 Geni Yanlış Anlam Mutasyonları Kedilerde Sebebi Bilinmeyen BöbrekHastalıkları İçin Önemli Olabilir mi?

Polikistik böbrek hastalığı (PKD), insanlarda otozomal resesif ve otozomal dominant olarak görülen heterojenik arkaplanı olan genetik bir hastalıktır. Kedilerde otozomal dominant PKD sıklıkla rapor edilirken, otozomal resesif PKDbildirilmemiştir. Tüm genom dizilemesi yapılmış olan siyam ırkı bir erkek kedide biyoinformatik analizler sonucunda PKHD1 geninde çeşitli yanlış anlam mutasyonları tespit edilmiştir. Bu Siyam ırkı kedinin kastrasyon için özel bir veteriner kliniğinegetirilmesinin ardından böbrek ve karaciğeri izlemek için geniş kan paneli yapıldı ve yüksek BUN ve kreatinin değerlerigözlendi. Ayrıca GPT değerinin de 2,5 kat olduğu belirlendi. Kedilerde nadiren PKD1 mutasyonundan bağımsız kistik böbrekvakaları bildirilmektedir. Ancak otozomal çekinik polikistik böbrek hastalığına neden olan genler için kedi genomları dahaönce incelenmemiştir. Bu çalışmada kedi genom verilerinde (n=100) otozomal resesif PKD’ye neden olan PKHD1 geniincelenmiştir. İnceleme sonucunda SIFT skoru yüksek 4 farklı mutasyon belirlenmiş ve bu mutasyonların PKHD1 genindenüretilen 7 transkriptte dur kodonu oluşumu ve dur kodonu kaybı ile sonuçlandığı ortaya konmuştur. Nadir hastalık olmasınıdestekler nitelikte, belirlenen mutasyonların frekanslarının 0.003, 0.001, 0.001 ve 0.003 olduğu hesaplanmıştır.

Could PKHD1 Gene Missense Mutations Be İmportant for İdiopathic Kidney Disease in Cats?

Polycystic kidney disease (PKD) is a genetic disease with a heterogeneous background seen in humans asautosomal recessive and autosomal dominant. While autosomal dominant PKD is frequently reported in cats, autosomalrecessive PKD has not been reported. Various missense mutations in the PKHD1 gene were detected as a result ofbioinformatic analyzes in a male cat whose whole genome was sequenced. After this Siamese cat was brought to a privateveterinary clinic for castration, a broad blood panel was performed to monitor kidney and liver, and elevated BUN andcreatinine values were observed. In addition, the GPT value was determined to be 2.5 times higher. Cases of cystic kidneyindependent of PKD1 mutation have been reported rarely in cats. However, cat genomes have not been previouslyexamined for genes that cause autosomal recessive polycystic kidney disease. In this study, the PKHD1 gene, which causesautosomal recessive PKD, was examined in cat genome data (n=100). As a result of the examination, four differentmutations with high SIFT scores were identified. These mutations resulted in stop codon formation and loss of stop codonsin 7 transcripts produced from the PKHD1 gene. The frequencies of the determined mutations were calculated to be 0.003,0.001, 0.001, and 0.003, which supports the fact that it is a rare disease.

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