Abstract
BackgroundMutations in the Inositol 1,4,5-Trisphosphate Receptor Type 1 (ITPR1) gene cause spinocerebellar ataxia type 29 (SCA29), a rare congenital-onset autosomal dominant non-progressive cerebellar ataxia. The Māori, indigenous to New Zealand, are an understudied population for genetic ataxias.Case presentationWe investigated the genetic origins of spinocerebellar ataxia in a family of Māori descent consisting of two affected sisters and their unaffected parents. Whole exome sequencing identified a pathogenic variant, p.Thr267Met, in ITPR1 in both sisters, establishing their diagnosis as SCA29.ConclusionsWe report the identification of a family of Māori descent with a mutation causing SCA29, extending the worldwide scope of this disease. Although this mutation has occurred de novo in other populations, suggesting a mutational hotspot, the children in this family inherited it from their unaffected mother who was germline mosaic.
Highlights
The autosomal dominant spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders that cause cerebellar ataxia and degeneration of the cerebellum and brainstem
Spinocerebellar ataxia type 29 (SCA29) is a rare congenital-onset autosomal dominant non-progressive cerebellar ataxia caused by mutations in the inositol 1,4,5-triphosphate receptor type 1 (ITPR1) gene characterized by early-onset hypotonia, gross motor delay, and mild cognitive impairment [2,3,4,5,6]
Patients have been reported with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) [14], hereditary spastic paraplegia type 7 [15], and autosomal recessive spastic ataxia of Charlevoix-Saguenay [16]
Summary
The autosomal dominant spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders that cause cerebellar ataxia and degeneration of the cerebellum and brainstem. Spinocerebellar ataxia type 29 (SCA29) is a rare congenital-onset autosomal dominant non-progressive cerebellar ataxia caused by mutations in the inositol 1,4,5-triphosphate receptor type 1 (ITPR1) gene characterized by early-onset hypotonia, gross motor delay, and mild cognitive impairment [2,3,4,5,6]. * Correspondence: bfogel@ucla.edu 1Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, 695 Charles E.
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