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Can a familial gastrointestinal tumour syndrome be allelic with Waardenburg syndrome?
MedLine Citation:
PMID:  20636395     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Vilain RE, Dudding T, Braye SG, Groombridge C, Meldrum C, Spigelman AD, Ackland S, Ashman L, Scott RJ. Can a familial gastrointestinal tumour syndrome be allelic with Waardenburg syndrome? 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.
Authors:
Re Vilain; T Dudding; Sg Braye; C Groombridge; C Meldrum; Ad Spigelman; S Ackland; L Ashman; Rj Scott
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical genetics     Volume:  79     ISSN:  1399-0004     ISO Abbreviation:  Clin. Genet.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-05     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0253664     Medline TA:  Clin Genet     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  554-60     Citation Subset:  IM    
Copyright Information:
© 2010 John Wiley & Sons A/S.
Affiliation:
Hunter Area Pathology Service, Hunter New England Health Service, Newcastle, NSW, Australia Hunter Genetics Unit, Hunter New England Health Service, Waratah, NSW, Australia Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Department of Medical Oncology, Newcastle Mater Misericordiae Hospital, Waratah, NSW, Australia School of Biomedical Sciences, University of Newcastle, Callaghan, NSW, Australia.
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