A novel intronic variant in UBE3A identified by genome sequencing in a patient with an atypical presentation of Angelman syndrome.
Am J Med Genet A
; 182(9): 2145-2151, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32652832
ABSTRACT
Angelman syndrome (AS) is a genetic neurodevelopmental disorder caused by loss or deficient expression of UBE3A on the maternally inherited allele. In 10-15% of individuals with a clinical diagnosis of AS, a molecular diagnosis cannot be established with conventional testing. We describe a 13-year-old male with an atypical presentation of AS, who was found to have a novel, maternally inherited, intronic variant in UBE3A (c.3-12T>A) using genome sequencing (GS). Targeted sequencing of RNA isolated from blood confirmed the creation of a new acceptor splice site. These GS results ended a six-year diagnostic odyssey and revealed a 50% recurrence risk for the unaffected parents. This case illustrates a previously unreported splicing variant causing AS. Intronic variants identifiable by GS may account for a proportion of individuals who are suspected of having well-known genetic disorders despite negative prior genetic testing.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Íntrons
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Síndrome de Angelman
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Predisposição Genética para Doença
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Ubiquitina-Proteína Ligases
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Child
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article