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SOS1 frameshift mutations cause pure mucosal neuroma syndrome, a clinical phenotype distinct from multiple endocrine neoplasia type 2B

Lookup NU author(s): Dr Paul Brennan


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BackgroundMucosal neuromas, thickened corneal nerves and marfanoid body habitus are characteristic phenotypic features of multiple endocrine neoplasia type 2B (MEN2B) and often provide an early clue to the diagnosis of the syndrome. Rarely, patients present with typical physical features of MEN2B but without associated endocrinopathies (medullary thyroid carcinoma or pheochromocytoma) or a RET gene mutation; this clinical presentation is thought to represent a distinct condition termed pure mucosal neuroma syndrome'.MethodsExome sequencing was performed in two unrelated probands with mucosal neuromas, thickened corneal nerves and marfanoid body habitus, but no MEN2B-associated endocrinopathy or RET gene mutation. Sanger sequencing was performed to confirm mutations detected by exome sequencing and to test in family members and 3 additional unrelated index patients with mucosal neuromas or thickened corneal nerves.ResultsA heterozygous SOS1 gene frameshift mutation (c.3266dup or c.3248dup) was identified in each proband. Sanger sequencing showed that proband 1 inherited the c.3266dup mutation from his affected mother, while the c.3248dup mutation had arisen de novo in proband 2. Sanger sequencing also identified one further novel SOS1 mutation (c.3254dup) in one of the 3 additional index patients.ConclusionOur results demonstrate the existence of pure mucosal neuroma syndrome as a clinical entity distinct from MEN2B that can now be diagnosed by genetic testing.

Publication metadata

Author(s): Owens M, Kivuva E, Quinn A, Brennan P, Caswell R, Allen HL, Vaidya B, Ellard S

Publication type: Article

Publication status: Published

Journal: Clinical Endocrinology

Year: 2016

Volume: 84

Issue: 5

Pages: 715-719

Print publication date: 01/05/2016

Online publication date: 04/02/2016

Acceptance date: 17/12/2015

ISSN (print): 0300-0664

ISSN (electronic): 1365-2265

Publisher: Wiley-Blackwell Publishing Ltd.


DOI: 10.1111/cen.13008


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Funder referenceFunder name
098395Wellcome Trust