Homozygous AHI1 gene mutation (c.1213A>C; Thr405Pro) leads to Joubert syndrome in a consanguineous Iranian family: A case report

Joubert syndrome (JS) is an autosomal recessive (AR) neurological disorder primarily characterized by aplasia/hypoplasia of the cerebellar vermis, retinal degeneration, and a molar tooth sign (MTS) can be seen on brain imaging. This study aimed to identify JS pathogenic variant in an Iranian consanguineous pedigree. We carried out whole-exome sequencing (WES) to identify likely causal pathogenic variant in the patient. The WES analysis identified a novel homozygous missense mutation (c.1213A>C; p.T405P) in the AHI1 gene (in exon 10). The Sanger sequencing data has validated the c.1213A>C mutation. We postulated that the disease in our patient was caused by a novel homozygous missense mutation in the AHI1 gene. To the best of our knowledge, this is the first report of the AHI1 pathogenic variant causing JS phenotype in an Iranian family. Our data expand the spectrum of mutations in the AHI1 gene in JS.