Long-Surviving Adult Siblings With Joubert Syndrome Harboring a Novel Compound Heterozygous Variant.

Background And Objectives: We describe 2 long-surviving siblings with a mild phenotype of Joubert syndrome (JBTS) harboring a novel compound heterozygous missense variant in the gene.

Methods: Targeted sequencing data of 2 middle-aged siblings (sister and brother) with JBTS were analyzed.

Results: The patients were older than 60 years and presented with an inborn facial anomaly and ataxia, accompanied by a molar tooth sign on brain MRI. The male patient showed mild intellectual disability, abnormal eye movements, and progressive gait disturbance. Targeted sequencing revealed a compound heterozygous missense variant of p.Arg1193Cys_Gln1223Pro; c.3577C>T_3668A>C. Multiple in silico assays predicted that the missense sites were pathogenic.

Discussion: The phenotype-genotype correlation of remains controversial, although many cases have been previously reported in children and young adults. Our study revealed a novel pathogenic variant of in patients, confirming the role of this gene in JBTS, thus providing an opportunity for neurologists to recognize JBTS as a differential diagnosis for chronic progressive ataxia in an aging society.