Authors
Motahareh Jadidi, Shima Booali, Kolsoum InanlooRahatloo
Published in
Molecular genetics and genomics : MGG. Volume 301. Issue 1. Jul 28, 2026. Epub Jul 28, 2026.
Abstract
Nephronophthisis type 4 (NPHP4) is a rare genetic kidney disorder progressing to end-stage renal disease (ESRD). In this study, we aimed to identify the genetic cause of NPHP4 in a pedigree with three affected individuals. Whole-exome sequencing was performed on the proband, and variants were filtered, analyzed, and evaluated using in silico tools. Co-segregation analysis was conducted using Sanger sequencing. Protein modeling for the wild-type and mutant forms was performed using AlphFold3. We identified a homozygous deletion (c.2999_3005delTGTGTGT/ p.Asn1000SerfsTer4) in exon 21 of NPHP4, which co-segregated with the disease in the pedigree, demonstrating an autosomal recessive inheritance. 3D protein modeling predicted significant structural changes due to the truncation. The results of this study reveal a deletion variant NPHP4 c.2999_3005del (p.Asn1000SerfsTer4) that causes NPHP4 disease. This study, as a second report of a variant, reaffirms this very variant's pathogenicity and illuminates a critical locus prone to disruption, enhancing our understanding of genotype-phenotype correlations in NPHP4. The concurrence of independent observations of the same variants in NPHP4 emphasizing C-terminal truncation strengthens evidence that disruption of this region is clinically relevant in NPHP4-related disease. These findings together can provide improved understanding of the genetic basis of the disease, therefore better guidance for genetic counseling and family planning strategies for additional affected families.
PMID:
42517941
Bibliographic data and abstract were imported from PubMed on 28 Jul 2026.
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