UBE2A deficiency in two siblings: A novel splicing variant inherited from a maternal germline mosaicism.
Am J Med Genet A
; 176(3): 722-726, 2018 Mar.
Article
em En
| MEDLINE
| ID: mdl-29283210
ABSTRACT
UBE2A deficiency is a syndromic condition of X-linked intellectual disability (ID) characterized by typical dysmorphic features that include synophrys, prominent supraorbital ridges, almond-shaped, and deep-set eyes, large ears, wide mouth, myxedematous appearance, hirsutism, micropenis, and onychodystrophy. To date, only seven familial UBE2A intragenic mutations and nine larger microdeletions encompassing UBE2A have been reported. Here, we describe two siblings with X-linked ID and typical clinical features of UBE2A deficiency caused by a novel hemizygous variant, identified by massively parallel sequencing of X-exome. The synonymous c.330G>A substitution in UBE2A modifies the last nucleotide of exon 5, causing the exon skipping and resulting in an out-of-frame transcript, likely encoding for a truncated form of the ubiquitin-conjugating enzyme E2 A. As confirmed by deep sequencing, the c.330G>A substitution in UBE2A was undetectable in genomic DNA from maternal blood cells, suggesting that the recurrent UBE2A deficiency observed in males of this family is caused by a maternal germline mosaicism.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Predisposição Genética para Doença
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Irmãos
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Enzimas de Conjugação de Ubiquitina
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Estudos de Associação Genética
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article