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Mutations in the IRBIT domain of ITPR1 are a frequent cause of autosomal dominant nonprogressive congenital ataxia
Author(s) -
Barresi S.,
Niceta M.,
Alfieri P.,
Brankovic V.,
Piccini G.,
Bruselles A.,
Barone M.R.,
Cusmai R.,
Tartaglia M.,
Bertini E.,
Zanni G.
Publication year - 2017
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12783
Subject(s) - ataxia , hypotonia , biology , mutation , spinocerebellar ataxia , genetics , phenotype , intellectual disability , cerebellar ataxia , exome sequencing , neuroscience , gene
Congenital ataxias are nonprogressive neurological disorders characterized by neonatal hypotonia, developmental delay and ataxia, variably associated with intellectual disability and other neurological or extraneurological features. We performed trio‐based whole‐exome sequencing of 12 families with congenital cerebellar and/or vermis atrophy in parallel with targeted next‐generation sequencing of known ataxia genes ( CACNA1A , ITPR1 , KCNC3 , ATP2B3 and GRM1 ) in 12 additional patients with a similar phenotype. Novel pathological mutations of ITPR1 (inositol 1,4,5‐trisphosphate receptor, type 1) were found in seven patients from four families (4/24, ∼16.8%) all localized in the IRBIT (inositol triphosphate receptor binding protein) domain which plays an essential role in the regulation of neuronal plasticity and development. Our study expands the mutational spectrum of ITPR1 ‐related congenital ataxia and indicates that ITPR1 gene screening should be implemented in this subgroup of ataxias.