Identification of novel and hotspot mutations in the channel domain of ITPR1 in two patients with Gillespie syndrome

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

ITPR1 encodes an intracellular receptor for inositol 1,4,5-trisphosphate (InsP3) which is highly expressed in the cerebellum and is involved in the regulation of Ca2 + homeostasis. Missense mutations in the InsP3-binding domain (IRBIT) of ITPR1 are frequently associated with early onset cerebellar atrophy. Gillespie syndrome is characterized by congenital ataxia, mild to moderate intellectual disability and iris hypoplasia. Dominant or recessive ITPR1 mutations have been recently associated with this form of syndromic ataxia. We performed next generation sequencing in two simplex families with Gillespie syndrome and identified de novo pathological mutations localized in the C-terminal channel domain of ITPR1 in both patients: a recurrent deletion (p.Lys2596del) and a novel missense mutation (p.Asn2576Ile) close to a point of constriction in the Ca2 + pore. Our study expands the mutational spectrum of ITPR1 and confirms that ITPR1 screening should be implemented in patients with congenital cerebellar ataxia with or without iris hypoplasia.
Original languageEnglish
Pages (from-to)141-145
Number of pages5
JournalGene
Volume628
DOIs
Publication statusPublished - Sep 10 2017

Fingerprint

Iris
Missense Mutation
Ataxia
Cerebellar Ataxia
Mutation
Inositol 1,4,5-Trisphosphate
Inositol
Constriction
Intellectual Disability
Cerebellum
Atrophy
Homeostasis
Aniridia cerebellar ataxia mental deficiency

Keywords

  • Cerebellar atrophy
  • Inositol 1,4,5 tri-phosphate receptor (InsP3) type 1 (ITPR1)
  • Intellectual disability
  • Partial aniridia

Cite this

@article{eb40930d334e469ba22c431d20ca0bfe,
title = "Identification of novel and hotspot mutations in the channel domain of ITPR1 in two patients with Gillespie syndrome",
abstract = "ITPR1 encodes an intracellular receptor for inositol 1,4,5-trisphosphate (InsP3) which is highly expressed in the cerebellum and is involved in the regulation of Ca2 + homeostasis. Missense mutations in the InsP3-binding domain (IRBIT) of ITPR1 are frequently associated with early onset cerebellar atrophy. Gillespie syndrome is characterized by congenital ataxia, mild to moderate intellectual disability and iris hypoplasia. Dominant or recessive ITPR1 mutations have been recently associated with this form of syndromic ataxia. We performed next generation sequencing in two simplex families with Gillespie syndrome and identified de novo pathological mutations localized in the C-terminal channel domain of ITPR1 in both patients: a recurrent deletion (p.Lys2596del) and a novel missense mutation (p.Asn2576Ile) close to a point of constriction in the Ca2 + pore. Our study expands the mutational spectrum of ITPR1 and confirms that ITPR1 screening should be implemented in patients with congenital cerebellar ataxia with or without iris hypoplasia.",
keywords = "Cerebellar atrophy, Inositol 1,4,5 tri-phosphate receptor (InsP3) type 1 (ITPR1), Intellectual disability, Partial aniridia",
author = "Dentici, {Maria Lisa} and Sabina Barresi and Marta Nardella and Emanuele Bellacchio and Paolo Alfieri and Alessandro Bruselles and Francesca Pantaleoni and Alberto Danieli and Giancarlo Iarossi and Marco Cappa and Enrico Bertini and Marco Tartaglia and Ginevra Zanni",
year = "2017",
month = "9",
day = "10",
doi = "10.1016/j.gene.2017.07.017",
language = "English",
volume = "628",
pages = "141--145",
journal = "Gene",
issn = "0378-1119",
publisher = "Elsevier B.V.",

}

TY - JOUR

T1 - Identification of novel and hotspot mutations in the channel domain of ITPR1 in two patients with Gillespie syndrome

AU - Dentici, Maria Lisa

AU - Barresi, Sabina

AU - Nardella, Marta

AU - Bellacchio, Emanuele

AU - Alfieri, Paolo

AU - Bruselles, Alessandro

AU - Pantaleoni, Francesca

AU - Danieli, Alberto

AU - Iarossi, Giancarlo

AU - Cappa, Marco

AU - Bertini, Enrico

AU - Tartaglia, Marco

AU - Zanni, Ginevra

PY - 2017/9/10

Y1 - 2017/9/10

N2 - ITPR1 encodes an intracellular receptor for inositol 1,4,5-trisphosphate (InsP3) which is highly expressed in the cerebellum and is involved in the regulation of Ca2 + homeostasis. Missense mutations in the InsP3-binding domain (IRBIT) of ITPR1 are frequently associated with early onset cerebellar atrophy. Gillespie syndrome is characterized by congenital ataxia, mild to moderate intellectual disability and iris hypoplasia. Dominant or recessive ITPR1 mutations have been recently associated with this form of syndromic ataxia. We performed next generation sequencing in two simplex families with Gillespie syndrome and identified de novo pathological mutations localized in the C-terminal channel domain of ITPR1 in both patients: a recurrent deletion (p.Lys2596del) and a novel missense mutation (p.Asn2576Ile) close to a point of constriction in the Ca2 + pore. Our study expands the mutational spectrum of ITPR1 and confirms that ITPR1 screening should be implemented in patients with congenital cerebellar ataxia with or without iris hypoplasia.

AB - ITPR1 encodes an intracellular receptor for inositol 1,4,5-trisphosphate (InsP3) which is highly expressed in the cerebellum and is involved in the regulation of Ca2 + homeostasis. Missense mutations in the InsP3-binding domain (IRBIT) of ITPR1 are frequently associated with early onset cerebellar atrophy. Gillespie syndrome is characterized by congenital ataxia, mild to moderate intellectual disability and iris hypoplasia. Dominant or recessive ITPR1 mutations have been recently associated with this form of syndromic ataxia. We performed next generation sequencing in two simplex families with Gillespie syndrome and identified de novo pathological mutations localized in the C-terminal channel domain of ITPR1 in both patients: a recurrent deletion (p.Lys2596del) and a novel missense mutation (p.Asn2576Ile) close to a point of constriction in the Ca2 + pore. Our study expands the mutational spectrum of ITPR1 and confirms that ITPR1 screening should be implemented in patients with congenital cerebellar ataxia with or without iris hypoplasia.

KW - Cerebellar atrophy

KW - Inositol 1,4,5 tri-phosphate receptor (InsP3) type 1 (ITPR1)

KW - Intellectual disability

KW - Partial aniridia

U2 - 10.1016/j.gene.2017.07.017

DO - 10.1016/j.gene.2017.07.017

M3 - Article

VL - 628

SP - 141

EP - 145

JO - Gene

JF - Gene

SN - 0378-1119

ER -