A de novo missense mutation in the inositol 1,4,5-triphosphate receptor type 1 gene causing severe pontine and cerebellar hypoplasia: Expanding the phenotype of ITPR1-related spinocerebellar ataxia's.

• 影响指数: 2.578
• 发表时间: Jan 2017
• 来源期刊: Am J Med Genet A
• DOI: 10.1002/ajmg.a.37962
• PMID: 27862915
• 文章类型: Case Reports
• 中科院分区: Q3
• 方向: 生物
• 作者列表: van Dijk T,Barth P,Reneman L,Appelhof B,Baas F,Poll-The BT

关键词: ITPR1 gene; pontocerebellar hypoplasia; spinocerebellar ataxia

Mesh: Alleles; Amino Acid Substitution; Cerebellum / abnormalities; Child; DNA Mutational Analysis; Developmental Disabilities / diagnosis genetics; Female; Genotype; High-Throughput Nucleotide Sequencing; Humans; Inositol 1,4,5-Trisphosphate Receptors / genetics; Magnetic Resonance Imaging / methods; Mutation, Missense; Nervous System Malformations / diagnosis genetics; Phenotype; Pons / abnormalities; Spinocerebellar Ataxias / diagnosis genetics

Abstract

We report a de novo missense mutation (c.7649T>A) in the inositol, 1,4,5 triphosphate receptor type 1 (ITPR1) gene in a patient with severe pontocerebellar hypoplasia. The mutation results in an amino acid substitution of a highly conserved isoleucine by asparagine (p. I2550N) in the transmembrane domain. Mutations and deletions of the ITPR1 gene are associated with several types of autosomal dominant spinocerebellar ataxia, varying in age of onset and severity. Patients have signs of cerebellar ataxia and at most, a mild cerebellar atrophy on MRI. In contrast, the patient we report here has profound cerebellar and pontine hypoplasia. Our finding therefore further expands the spectrum of ITPR1-related ataxias. © 2016 Wiley Periodicals, Inc.