Genetic and clinical landscape of childhood cerebellar hypoplasia and atrophy

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art_SAKAMOTO_Genetic_and_clinical_landscape_of_childhood_cerebellar_hypoplasia_2022.PDF (1.45 MB)
Citações na Scopus
1
Tipo de produção
article
Data de publicação
2022
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER SCIENCE INC
Autores
SAKAMOTO, Masamune
IWAMA, Kazuhiro
SASAKI, Masayuki
ISHIYAMA, Akihiko
KOMAKI, Hirofumi
SAITO, Takashi
TAKESHITA, Eri
SHIMIZU-MOTOHASHI, Yuko
HAGINOYA, Kazuhiro
KOBAYASHI, Tomoko
Citação
GENETICS IN MEDICINE, v.24, n.12, p.2453-2463, 2022
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Purpose: Cerebellar hypoplasia and atrophy (CBHA) in children is an extremely heterogeneous group of disorders, but few comprehensive genetic studies have been reported. Comprehensive genetic analysis of CBHA patients may help differentiating atrophy and hypoplasia and potentially improve their prognostic aspects. Methods: Patients with CBHA in 176 families were genetically examined using exome sequencing. Patients with disease-causing variants were clinically evaluated. Results: Disease-causing variants were identified in 96 of the 176 families (54.5%). After excluding 6 families, 48 patients from 42 families were categorized as having syndromic associations with CBHA, whereas the remaining 51 patients from 48 families had isolated CBHA. In 51 patients, 26 aberrant genes were identified, of which, 20 (76.9%) caused disease in 1 family each. The most prevalent genes were CACNA1A, ITPR1, and KIF1A. Of the 26 aberrant genes, 21 and 1 were functionally annotated to atrophy and hypoplasia, respectively. CBHA+S was more clinically severe than CBHA-S. Notably, ARG1 and FOLR1 variants were identified in 2 families, leading to medical treatments. Conclusion: A wide genetic and clinical diversity of CBHA was revealed through exome sequencing in this cohort, which highlights the importance of comprehensive genetic analyses. Furthermore, molecular-based treatment was available for 2 families.
Palavras-chave
Cerebellar atrophy, Cerebellar hypoplasia, Disease-causing variants, Exome, Treatment
URI
https://observatorio.fm.usp.br/handle/OPI/53031
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MPE
Artigos e Materiais de Revistas Científicas - LIM/36