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Cys 618 Arg mutation in the RET proto‐oncogene associated with familial medullary thyroid carcinoma and maternally transmitted Hirschsprung's disease suggesting a role for imprinting
Author(s) -
Peretz Hava,
Luboshitsky Rafael,
Baron Ela,
Biton Am,
Gershoni Ruth,
Usher Saly,
Grynberg Elisheva,
Yakobson Emanuel,
Graff Eran,
Lapidot Mordechai
Publication year - 1997
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1997)10:2<155::aid-humu7>3.0.co;2-j
Subject(s) - ret proto oncogene , multiple endocrine neoplasia type 2 , biology , pheochromocytoma , thyroid carcinoma , hirschsprung's disease , mutation , genetics , proto oncogene proteins c ret , allele , cancer research , multiple endocrine neoplasia , medullary thyroid cancer , haplotype , disease , medicine , endocrinology , thyroid , germline mutation , gene , receptor , neurotrophic factors , glial cell line derived neurotrophic factor
The multiple endocrine neoplasia type 2 (MEN2) syndromes and Hirschsprung's disease (HSCR) are inherited neurocristopathies characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, parathyroid disease, and gastrointestinal neuromatosis. Mutations in the RET proto‐oncogene are the underlying cause of the MEN2 syndromes and some cases of HSCR. In this report, we show that Cys 618 Arg mutation cosegregates with familial MTC and HSCR in two Moroccan Jewish families in which no involvement of pheochromocytoma or parathyroidism was observed. A single haplotype shared by chromosomes bearing the Cys 618 Arg mutation in both families strongly suggests a founder effect for this mutation. We have observed in our and in several other previously reported families, an excess of maternal over paternal mutated RET alleles in offsprings affected by HSCR. We suggest that parental imprinting may play a role in the ethiology of HSCR caused by mutations in the RET protooncogene. Hum Mutat 10:155–159, 1997. © 1997 Wiley‐Liss, Inc.