Can a familial gastrointestinal tumour syndrome be allelic with Waardenburg syndrome?
Clin Genet
; 79(6): 554-60, 2011 Jun.
Article
em En
| MEDLINE
| ID: mdl-20636395
ABSTRACT
Familial gastrointestinal stromal tumours (GISTs) are rare but otherwise well-characterized tumour syndromes, most commonly occurring on a background of germline-activating mutations in the tyrosine kinase receptor c-KIT. The associated clinical spectrum reflects the constitutive activation of this gene product across a number of cell lines, generating gain-of-function phenotypes in interstitial cells of Cajal (GIST and dysphagia), mast cells (mastocytosis) and melanocytes (hyperpigmentation). We report a three-generation kindred harbouring a c-KIT germline-activating mutation resulting in multifocal GISTs, dysphagia and a complex melanocyte hyperpigmentation and hypopigmentation disorder, the latter with features typical of those observed in Waardenburg type 2 syndrome (WS2F). Sequencing of genes known to be causative for WS [microphthalmia transcription factor (MITF), Pax3, Sox10, SNAI2 ] failed to show any candidate mutations to explain this complex cutaneous depigmentation phenotype. Our case report conclusively expands the clinical spectrum of familial GISTs and shows a hitherto unrecognized link to WS. Possible mechanisms responsible for this novel cause of WS2F will be discussed.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Waardenburg
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Síndromes Neoplásicas Hereditárias
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Tumores do Estroma Gastrointestinal
Limite:
Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Genet
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Austrália