Long-Surviving Adult Siblings With Joubert Syndrome Harboring a Novel Compound Heterozygous CPLANE1 Variant. (26th October 2022)

• Record Type: Journal Article
• Authors: Matoba, Kento; Chihara, Norio; Satake, Wataru; Tokuoka, Hideki; Otsuka, Yoshihisa; Ueda, Takehiro; Sekiguchi, Kenji; Itoh, Masayuki; Matsumoto, Riki
• Is Part Of: Neurology. Volume 8:Number 5(2022)
• Publication Date: 2022-10-26
• Subjects: Neurogenetics -- Periodicals; 616.80442
• DOI: 10.1212/NXG.0000000000200031
• Languages: English
• ISSNs: 2376-7839

Abstract

Abstract : 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 CPLANE1 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 CPLANE1 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 CPLANE1 remains controversial, although many cases have been previously reported in children and young adults. Our study revealed a novel pathogenic variant of CPLANE1 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.