Long-Surviving Adult Siblings With Joubert Syndrome Harboring a Novel Compound Heterozygous CPLANE1 Variant

Kento Matoba; Norio Chihara; Wataru Satake; Hideki Tokuoka; Yoshihisa Otsuka; Takehiro Ueda; Kenji Sekiguchi; Masayuki Itoh; Riki Matsumoto

doi:10.1212/NXG.0000000000200031

Long-Surviving Adult Siblings With Joubert Syndrome Harboring a Novel Compound Heterozygous CPLANE1 Variant

Neurol Genet. 2022 Sep 26;8(5):e200031. doi: 10.1212/NXG.0000000000200031. eCollection 2022 Oct.

Authors

Kento Matoba¹, Norio Chihara¹, Wataru Satake¹, Hideki Tokuoka¹, Yoshihisa Otsuka¹, Takehiro Ueda¹, Kenji Sekiguchi¹, Masayuki Itoh¹, Riki Matsumoto¹

Affiliation

¹ Division of Neurology (K.M, N.C., H.T., Y.O., T.U., K.S., R.M.), Kobe University Graduate School of Medicine, Kobe; Department of Neurology (W.S.), Graduate School of Medicine, The University of Tokyo; and Department of Mental Retardation and Birth Defect Research (M.I.), National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.

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.