Mutations in the IRBIT domain of ITPR1 are a frequent cause of autosomal dominant nonprogressive congenital ataxia

被引：27

作者：

Barresi, S. ^{[1
,2
]}

Niceta, M. ^{[2
]}

Alfieri, P. ^{[3
]}

Brankovic, V. ^{[4
]}

Piccini, G. ^{[3
]}

Bruselles, A. ^{[5
]}

Barone, M. R. ^{[6
]}

Cusmai, R. ^{[7
]}

Tartaglia, M. ^{[2
]}

Bertini, E. ^{[1
]}

Zanni, G. ^{[1
]}

机构：

[1] IRCCS, Bambino Gesu Childrens Hosp, Dept Neurosci, Unit Mol Med Neuromuscular & Neurodegenerat Disor, Rome, Italy

[2] IRCCS, Bambino Gesu Childrens Hosp, Genet & Rare Dis Res Div, Rome, Italy

[3] IRCCS, Bambino Gesu Childrens Hosp, Child Neuropsychiat, Dept Neurosci, Rome, Italy

[4] Univ Belgrade, Fac Med, Clin Child Neurol & Psychiat, Belgrade, Serbia

[5] Ist Super Sanita, Dept Hematol Oncol & Mol Med, Rome, Italy

[6] Fdn Betania Onlus, Ctr Ambulatoriale Riabilitaz, Catanzaro, Italy

[7] IRCCS, Bambino Gesu Childrens Hosp, Neurol, Dept Neurosci, Rome, Italy

来源：

CLINICAL GENETICS | 2017年 / 91卷 / 01期

关键词：

cerebellar atrophy; congenital ataxia; IRBIT domain; ITPR1; targeted resequencing; WES; CEREBELLAR-ATAXIA; MISSENSE MUTATIONS; RECEPTOR; DELETION; IP3;

D O I：

10.1111/cge.12783

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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, similar to 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.

引用

页码：86 / 91

页数：6

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