title: 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.
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.
authors.affiliation: Department of Clinical Genetics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Tessa
authors.initials: T
authors.lastname: van Dijk
authors.affiliation: Department of Pediatric Neurology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Barth
authors.affiliation: Department of Radiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Reneman
authors.affiliation: Department of Clinical Genetics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Appelhof
authors.affiliation: Department of Clinical Genetics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Baas
authors.affiliation: Department of Pediatric Neurology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Bwee Tien
authors.initials: BT
authors.lastname: Poll-The
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D002531:Cerebellum / Q000002:abnormalities*; D002648:Child; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics*; D008279:Magnetic Resonance Imaging / Q000379:methods; D020125:Mutation, Missense; D009421:Nervous System Malformations / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D011149:Pons / Q000002:abnormalities*; D020754:Spinocerebellar Ataxias / Q000175:diagnosis / Q000235:genetics
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors
keywords: ITPR1 gene; pontocerebellar hypoplasia; spinocerebellar ataxia