A novel 1.38-kb deletion combined with a single nucleotide variant in KIAA0586 as a cause of Joubert syndrome

Abstract

Abstract Background: KIAA0586, also known as Talplid3, plays critical roles in primary cilia formation and hedgehog signaling in humans. Variants in KIAA0586 could cause some different ciliopathies, including Joubert syndrome (JBTS), which is a clinically and genetically heterogeneous group of autosomal recessive neurological disorders. Methods and Results: A 9-month-old girl was diagnosed as JBTS by the “molar tooth sign” of the mid-brain and global developmental delay. By whole-exome sequencing, we identified a single nucleotide variant c.3303G>A and a 1.38-kb deletion in KIAA0586 in the proband. These two variants of KIAA0586 were consistent with the mode of autosomal recessive inheritance in the family, which was verified using Sanger sequencing. Conclusions: This finding of a compound heterozygote with a 1.38-kb deletion and c.3303G>A gave a precise genetic diagnosis for the patient, and the novel 1.38-kb deletion also expanded the pathogenic variation spectrum of JBTS caused by KIAA0586.