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Can a familial gastrointestinal tumour syndrome be allelic with Waardenburg syndrome?
Author(s) -
Vilain RE,
Dudding T,
Braye SG,
Groombridge C,
Meldrum C,
Spigelman AD,
Ackland S,
Ashman L,
Scott RJ
Publication year - 2011
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2010.01489.x
Subject(s) - waardenburg syndrome , microphthalmia associated transcription factor , pax3 , genetics , germline mutation , biology , pigmentation disorder , cancer research , medicine , pathology , mutation , phenotype , gene , transcription factor
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.