A RAB27A duplication in several cases of Griscelli syndrome type 2: An explanation for cases lacking a genetic diagnosis.
Hum Mutat
; 38(10): 1355-1359, 2017 10.
Article
em En
| MEDLINE
| ID: mdl-28585352
ABSTRACT
Griscelli syndrome type 2 (GS2) is a rare and often fatal autosomal recessive, hyperinflammatory disorder. It is associated with hypopigmentation of the skin and the hair, resulting in the characteristic pigment accumulation and clumping in the hair shaft. Loss-of-function mutations in RAB27A, resulting from point mutations, short indel, or large deletions, account for all the cases reported to date. However, several GS2 cases originating from Saudi Arabia lack a genetic diagnosis. Here, we report on a new RAB27A genetic anomaly observed in seven Saudi Arabia families that had remained negative after extensive molecular genomic DNA testing. Linkage analysis and targeted sequencing of the RAB27A genomic region in several of these patients led to the identification of a common homozygous tandem duplication of 38 kb affecting exon 2-5 and resulting in a premature stop codon. The pathogenic effect of this duplication was confirmed by a cDNA analysis and functional assays. The identification of microhomology flanking the breakpoint site suggests a possible underlying mechanism.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piebaldismo
/
Hipopigmentação
/
Linfo-Histiocitose Hemofagocítica
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Proteínas rab27 de Ligação ao GTP
/
Síndromes de Imunodeficiência
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Female
/
Humans
/
Male
País/Região como assunto:
Asia
Idioma:
En
Revista:
Hum Mutat
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
França