Exome sequencing reveals three homozygous missense variants in SNRPA in two sisters with syndromic intellectual disability.
Clin Genet
; 93(6): 1229-1233, 2018 06.
Article
em En
| MEDLINE
| ID: mdl-29437235
ABSTRACT
Splicing-related gene mutations might affect the expression of a single gene or multiple genes and cause clinically heterogeneous diseases. With the advent of next-generation sequencing, several splicing gene mutations have been exposed, yet most major spliceosome genes have no reports of germline mutations and therefore, their effects are largely unknown. We describe the previously unreported concurrence of intellectual disability, short stature, poor speech, and minor craniofacial and hand anomalies in 2 female siblings with 3 homozygous missense variants in SNRPA (a component of the U1 small nuclear ribonucleoprotein complex) characterized by homozygosity mapping and whole exome sequencing. Combined, c.97A>G, c.98T>C, and c.100T>A, in exon 2 of SNRPA lead to p.Ile33Ala and p.Phe34Ile exchanges, which were predicted in silico to be deleterious. Although both patients exhibited some clinical features seen in other spliceosomal disorders, their complete clinical phenotype appears to be rather uncommon, a finding that may further support the notion that mutations in components of the major spliceosome do not strictly lead to the same syndromes/phenotypes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ribonucleoproteína Nuclear Pequena U1
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Mutação de Sentido Incorreto
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Irmãos
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Sequenciamento do Exoma
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Deficiência Intelectual
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Child
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Child, preschool
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Female
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Humans
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Newborn
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article