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Autosomal recessive distal renal tubular acidosis (dRTA) has been linked to biallelic mutations in WDR72 (Gene Symbol; MONDO_0001909). Whole‐exome sequencing in a family with three affected siblings identified compound heterozygous variants c.1777A>G (p.Arg593Gly) and c.2522T>A (p.Leu841Gln) that segregated with early‐onset metabolic acidosis and nephrocalcinosis (PMID:30028003). In a second unrelated family, a homozygous nonsense variant c.2686C>T (p.Arg896Ter) was found in an individual with dRTA, further supporting causality (PMID:30028003).
In silico structural modeling demonstrated that p.Arg593Gly and p.Leu841Gln disrupt key hydrogen‐bond networks within WDR72, predicting loss of function consistent with impaired distal acid secretion (PMID:30028003). No functional rescue models have yet been reported. These data constitute limited but consistent genetic and computational evidence for WDR72 as a novel dRTA gene.
Key Take-home: WDR72 should be considered in the genetic workup of autosomal recessive distal RTA, particularly when known dRTA gene panels are negative.
Gene–Disease AssociationLimitedFour affected individuals from two families with autosomal recessive segregation and absence in controls ([PMID:30028003]) Genetic EvidenceLimitedCompound heterozygous and homozygous WDR72 variants in four cases across two families (segregation in three siblings + one independent family) ([PMID:30028003]) Functional EvidenceLimitedIn silico modeling predicts structural disruption of WDR72 affecting acidification function ([PMID:30028003]) |