Clinical and molecular mechanistic insights into the WDR72 mutation.

Abstract

Distal renal tubular acidosis (dRTA) is a rare kidney disorder with an incidence of less than 1 in 100 000 people, characterised by metabolic acidosis and hypokalaemia. While mutations in genes such as ATP6V1B1, ATP6V0A4 and SLC4A1 are commonly associated with dRTA, this study reports a rare variant of the WDR72 gene in siblings from the Punjabi population in India. The individuals exhibited amelogenesis imperfecta (AI), hypokalaemic periodic paralysis (HPP) and acidaemia due to impaired ion transport in the distal convoluted tubule. Genetic testing revealed novel variants in the WDR72 gene: c.2934G>A, p.Trp978 and c.781G>A, p.Gly261Arg. Researchers observed a positive therapeutic response following potassium supplementation. This study highlights a rare WDR72 variant associated with AI, dRTA and HPP, and explores the potential underlying molecular mechanisms.