Copy Number Variant Analysis of Spinocerebellar Ataxia Genes in a Cohort of Dutch Patients With Cerebellar Ataxia.

Ghorbani, Fatemeh; de Boer, Eddy N; Benjamins-Stok, Marloes; Verschuuren-Bemelmans, Corien C; Knapper, Jurjen; de Boer-Bergsma, Jelkje; de Vries, Jeroen J; Sikkema-Raddatz, Birgit; Verbeek, Dineke S; Westers, Helga; van Diemen, Cleo C

Ghorbani, Fatemeh; de Boer, Eddy N; Benjamins-Stok, Marloes; Verschuuren-Bemelmans, Corien C; Knapper, Jurjen; de Boer-Bergsma, Jelkje; de Vries, Jeroen J; Sikkema-Raddatz, Birgit; Verbeek, Dineke S; Westers, Helga; van Diemen, Cleo C.

Afiliação

Ghorbani F; From the Department of Genetics (F.G., E.N.d.B., M.B.-S., C.C.V.-B., J.K., J.d.B.-B., B.S.-R., D.S.V., H.W., C.C.v.D.), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; and Department of Neurology (J.J.d.V.), University Medical Center Groningen, University of
de Boer EN; From the Department of Genetics (F.G., E.N.d.B., M.B.-S., C.C.V.-B., J.K., J.d.B.-B., B.S.-R., D.S.V., H.W., C.C.v.D.), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; and Department of Neurology (J.J.d.V.), University Medical Center Groningen, University of
Benjamins-Stok M; From the Department of Genetics (F.G., E.N.d.B., M.B.-S., C.C.V.-B., J.K., J.d.B.-B., B.S.-R., D.S.V., H.W., C.C.v.D.), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; and Department of Neurology (J.J.d.V.), University Medical Center Groningen, University of
Verschuuren-Bemelmans CC; From the Department of Genetics (F.G., E.N.d.B., M.B.-S., C.C.V.-B., J.K., J.d.B.-B., B.S.-R., D.S.V., H.W., C.C.v.D.), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; and Department of Neurology (J.J.d.V.), University Medical Center Groningen, University of
Knapper J; From the Department of Genetics (F.G., E.N.d.B., M.B.-S., C.C.V.-B., J.K., J.d.B.-B., B.S.-R., D.S.V., H.W., C.C.v.D.), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; and Department of Neurology (J.J.d.V.), University Medical Center Groningen, University of
de Boer-Bergsma J; From the Department of Genetics (F.G., E.N.d.B., M.B.-S., C.C.V.-B., J.K., J.d.B.-B., B.S.-R., D.S.V., H.W., C.C.v.D.), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; and Department of Neurology (J.J.d.V.), University Medical Center Groningen, University of
de Vries JJ; From the Department of Genetics (F.G., E.N.d.B., M.B.-S., C.C.V.-B., J.K., J.d.B.-B., B.S.-R., D.S.V., H.W., C.C.v.D.), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; and Department of Neurology (J.J.d.V.), University Medical Center Groningen, University of
Sikkema-Raddatz B; From the Department of Genetics (F.G., E.N.d.B., M.B.-S., C.C.V.-B., J.K., J.d.B.-B., B.S.-R., D.S.V., H.W., C.C.v.D.), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; and Department of Neurology (J.J.d.V.), University Medical Center Groningen, University of
Verbeek DS; From the Department of Genetics (F.G., E.N.d.B., M.B.-S., C.C.V.-B., J.K., J.d.B.-B., B.S.-R., D.S.V., H.W., C.C.v.D.), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; and Department of Neurology (J.J.d.V.), University Medical Center Groningen, University of
Westers H; From the Department of Genetics (F.G., E.N.d.B., M.B.-S., C.C.V.-B., J.K., J.d.B.-B., B.S.-R., D.S.V., H.W., C.C.v.D.), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; and Department of Neurology (J.J.d.V.), University Medical Center Groningen, University of
van Diemen CC; From the Department of Genetics (F.G., E.N.d.B., M.B.-S., C.C.V.-B., J.K., J.d.B.-B., B.S.-R., D.S.V., H.W., C.C.v.D.), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; and Department of Neurology (J.J.d.V.), University Medical Center Groningen, University of

Neurol Genet ; 9(1): e200050, 2023 Feb.

Article em En | MEDLINE | ID: mdl-38058854

RESUMO

Background and Objectives: The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of neurodegenerative disorders generally caused by single nucleotide variants (SNVs) or indels in coding regions or by repeat expansions in coding and noncoding regions of SCA genes. Copy number variants (CNVs) have now also been reported for 3 genes-ITPR1, FGF14, and SPTBN2-but not all SCA genes have been screened for CNVs as the underlying cause of the disease in patients. In this study, we aim to assess the prevalence of CNVs encompassing 36 known SCA genes. Methods: A cohort of patients with cerebellar ataxia who were referred to the University Medical Center Groningen for SCA genetic diagnostics was selected for this study. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed using the Infinium Global Screening Array. Following data processing, genotyping data were uploaded into NxClinical software to perform CNV analysis per patient and to visualize identified CNVs in 36 genes with allocated SCA symbols. The clinical relevance of detected CNVs was determined using evidence from studies based on PubMed literature searches for similar CNVs and phenotypic features. Results: Of the 338 patients with cerebellar ataxia, we identified putative clinically relevant CNV deletions in 3 patients: an identical deletion encompassing ITPR1 in 2 patients, who turned out to be related, and a deletion involving PPP2R2B in another patient. Although the CNV deletion in ITPR1 was clearly the underlying cause of SCA15 in the 2 related patients, the clinical significance of the deletion in PPP2R2B remained unknown. Discussion: We showed that CNVs detectable with the limited resolution of SNP array are a very rare cause of SCA. Nevertheless, we suggest adding CNV analysis alongside SNV analysis to SCA gene diagnostics using next-generation sequencing approaches, at least for ITPR1, to improve the genetic diagnostics for patients.

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Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: Neurol Genet Ano de publicação: 2023 Tipo de documento: Article