Open AccessA Homozygous Missense Variant in INPP5E Associated with Joubert Syndrome and Related Disorders
Author(s) -
Mitesh Shetty,
Nimmy Ramdas,
Shubhi Sahni,
Nandita Mullapudi,
Shivanand Hegde
Publication year - 2017
Publication title -
molecular syndromology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.609
H-Index - 36
eISSN - 1661-8777
pISSN - 1661-8769
DOI - 10.1159/000479673
Subject(s) - joubert syndrome , missense mutation , medicine , genetics , pediatrics , biology , mutation , gene
Joubert syndrome and related disorders (JSRD; ORPHA 140874) is a complex set of neurodevelopmental disorders with multiple organ involvement. JSRD is a type of ciliopathy which is caused by the presence of defective primary cilia in an individual. JSRD is commonly inherited in an autosomal recessive pattern, and more than 23 genes are known to be associated with JSRD. We report a novel homozygous mutation identified in the INPP5E gene, c.1303C>T, which leads to a change of an amino acid from arginine to tryptophan at residue 435 in the protein chain. In silico analysis indicates that p.Arg435Trp substitution affects the functionality of the protein product of the gene. Our result adds to the growing body of evidences that underlines the clinical utility of next-generation sequencing in the diagnosis of a genetic disorder when clinical features are inconclusive.