Identification of PDIA6 Mutation in a Case of Autosomal Recessive Polycystic Kidney Disease: A Case Report and Review of Literature.

Abstract

Autosomal recessive polycystic kidney disease (ARPKD) is a rare but severe hereditary renal disorder characterized by bilaterally enlarged, cystic kidneys and varying degrees of hepatic fibrosis, often leading to early-onset kidney failure and significant morbidity. While most ARPKD cases are linked to mutations in the PKHD1 gene, recent advances in genomic sequencing have revealed that mutations in other genes, including PDIA6, may contribute to similar phenotypes. The PDIA6 gene encodes protein disulfide isomerase A6, which plays a critical role in protein folding within the endoplasmic reticulum (ER) and in the regulation of ER stress responses. Here, we report a rare and complex case of a full-term male neonate born to consanguineous Syrian refugee parents, who presented with a clinical constellation of features including polycystic kidney disease, severe oligohydramnios, pulmonary hypoplasia, microcephaly, rib thoracic dysplasia, and global developmental delay. Genetic analysis using whole-exome sequencing identified a homozygous two-base deletion in exon 5 of the PDIA6, resulting in a premature stop codon. Early diagnosis via genomic tools is essential for prognosis, management, and genetic counseling.