Clinical and Molecular Delineation of AHI1-Associated Joubert Syndrome in a Consanguineous Pedigree: A Case Report

Joubert syndrome (JS) is a rare autosomal recessive neurodevelopmental disorder characterized by the molar tooth sign (MTS) on brain magnetic resonance imaging (MRI), resulting from cerebellar vermis hypoplasia and elongated superior cerebellar peduncles. A 4-year-old female presenting with global developmental delay, hypotonia, oculomotor apraxia, and MTS on MRI underwent whole-exome sequencing (WES). Bioinformatic analysis, Sanger validation, and segregation studies were performed. Pathogenicity was assessed using ACMG/AMP guidelines and in silico tools. WES revealed a novel homozygous nonsense variant in AHI1 (c.2938A>T; p.Lys980Ter), absent in population databases. Segregation analysis confirmed autosomal recessive inheritance, with both parents as heterozygous carriers. Evolutionary conservation of Lys980 underscored its functional importance. This study expands the mutational spectrum of AHI1-related JS and highlights the utility of WES in consanguineous populations. The findings facilitate precise diagnosis, genetic counseling, and informed reproductive planning for at-risk families.