Biallelic Mutations in <b><i>DNAJB11</i></b>are Associated with Prenatal Polycystic Kidney Disease in a Turkish Family

Abstract

Polycystic kidney disease (PKD) is a life-threatening condition resulting in end-stage renal disease. Two major forms of PKD are defined according to the inheritance pattern. Autosomal dominant PKD (ADPKD) is characterized by renal cysts, where nearly half of the patients suffers from renal failure in the 7th decade of life. Autosomal recessive PKD (ARPKD) is a rarer and more severe form presenting in childhood. Whole-exome sequencing (WES) analyses was performed to investigate molecular causes of the disease in the fetus. In this study, we present 2 fetuses prenatally diagnosed with PKD in a consanguineous family. WES analysis of the second fetus revealed a homozygous variant (c.740+1G&amp;#x3e;A) in &lt;i&gt;DNAJB11&lt;/i&gt; which is related to ADPKD. This study reveals that &lt;i&gt;DNAJB11&lt;/i&gt; biallelic mutations may cause an antenatal severe form of ARPKD and contributes to understanding the &lt;i&gt;DNAJB11&lt;/i&gt;-related ADPKD phenotype. The possibility of ARPKD due to biallelic mutations in ADPKD genes should be considered in genetic counseling.

Monoallelic IFT140 pathogenic variants are an important cause of the autosomal dominant polycystic kidney-spectrum phenotype

“…[79][80][81] Monoallelic PKHD1 pathogenic variants can be associated with mild PKD/PLD, and recently bi-allelic DNAJB11 variants have been associated with an ARPKDlike disease with pancreatic cysts. 14,25,82,83 Bi-allelic variants to ALG9, or the ADPLD-associated ALG8 (MIM: 608103), cause congenital defects of glycosylation (CDG1L and CDG1H, respectively), that involve cystic kidneys as part of severe, developmental disorders. 84,85 In many of these disorders, including the association of biallelic IFT140 variants with SRTD, two LoF variants are probably not compatible with life (viable individuals have at least one nontruncating variant).…”