Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 141-145 |
| Number of pages | 5 |
| Journal | Gene |
| Volume | 628 |
| DOIs | |
| Publication status | Published - Sep 10 2017 |
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Keywords
- Cerebellar atrophy
- Inositol 1,4,5 tri-phosphate receptor (InsP3) type 1 (ITPR1)
- Intellectual disability
- Partial aniridia
Cite this
Identification of novel and hotspot mutations in the channel domain of ITPR1 in two patients with Gillespie syndrome. / Dentici, Maria Lisa; Barresi, Sabina; Nardella, Marta; Bellacchio, Emanuele; Alfieri, Paolo; Bruselles, Alessandro; Pantaleoni, Francesca; Danieli, Alberto; Iarossi, Giancarlo; Cappa, Marco; Bertini, Enrico; Tartaglia, Marco; Zanni, Ginevra.
In: Gene, Vol. 628, 10.09.2017, p. 141-145.Research output: Contribution to journal › Article
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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 -