GANAB and PKD1 Variations in a 12 Years Old Female Patient With Early Onset of Autosomal Dominant Polycystic Kidney Disease

• Published in: Frontiers in genetics Vol. 10; p. 44
• Main Authors: Waldrop, Elizabeth, Al-Obaide, Mohammed A I, Vasylyeva, Tetyana L
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 07.02.2019
• Subjects: autosomal dominant polycystic kidney disease; Genetics; glucosidase II alpha subunit; missense mutation; nonsense mutation; polycystin-1; transcription factors binding sites; nonsense mutation; polycystin-1; glucosidase II alpha subunit; autosomal dominant polycystic kidney disease; transcription factors binding sites; missense mutation
• ISSN: 1664-8021; 1664-8021
• DOI: 10.3389/fgene.2019.00044

Autosomal Dominant Polycystic Kidney Disease (ADPKD) typically results from a mutation in the PKD1 and PKD2 genes, which code for polycystin-1 (PC1) and polycystin-2 (PC2), respectively. Mutations in these genes promote renal cystic dysplasia and are a significant cause of End-Stage Kidney Disease (ESKD). Polycystic kidney disease-3 (PKD3), another form of ADPKD, is caused by mutations in glucosidase II alpha subunit (GANAB) gene and present in mid- and late adulthood. We report a description of an ADPKD case in a 12-year-old female presented bilateral renal cysts in adolescence. Two mutations in two genes PKD1 and GANAB were identified by targeted capture and next-generation sequencing (NGS) on an Illumina sequencing system. The identified PKD1 mutation p.Pro61Leu: c.182C > T (CCC > CTC) a missense type of uncertain clinical significance. However, the identified PKD1 mutation can alter transcription factors motifs and consequently disturb the transcription process. The second mutation identified in GANAB locus, p.Arg61Ter: c.181C > T, a nonsense type, CGA > TGA. The mutation is unreported pathogenic variant can cause loss of the glucosidase II alpha subunit normal protein function. Both the patient father and paternal grandmother had a history of ADPKD but never were tested. This case is the first case of combine presentation on PKD1 and PKD3 in a pediatric patient with nephrolithiasis.