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9111176 
Journal Article 
A RET double mutation in the germline of a kindred with FMTC 
Bartsch, DK; Hasse, C; Schug, C; Barth, P; Rothmund, M; Hoppner, W; , 
2000 
Yes 
Experimental and Clinical Endocrinology & Diabetes
ISSN: 0947-7349
EISSN: 1439-3646 
JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH 
STUTTGART 
128-132 
English 
10826520 
WOS:000086775700011 
Activating germline mutations of the RET proto-oncogene are found in more than 90% of families with multiple endocrine neoplasia type 2a (MEN 2a) and familial medullary thyroid carcinoma (FMTC). The majority of patients with these hereditary tumors carry germline mutations that result in the substitution of one of five cysteine residues in exon 10 and 11. Different mutations in exons 13, 14 and 15 affecting non-cysteine residues have also been described but are considered to be rare. We now for the first time report a double mutation of the RET proto-oncogene occurring in the germline of a kindred with FMTC. Both mutations occur within the tyrosine kinase domain in exon 14 and lead to the substitution of valine 804 by methionine and arginine 844 by leucine. Since the double mutated allele cosegregated with the disease and was not identified in 200 unrelated normal probands, we conclude that they represent mutations that predispose the individual to the development of FMTC with a mild phenotype.