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.

Abstract	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.
Authors	H Peretz, R Luboshitsky, E Baron, A Biton, R Gershoni, S Usher, E Grynberg, E Yakobson, E Graff, M Lapidot
Journal	Human mutation (Hum Mutat) Vol. 10 Issue 2 Pg. 155-9 ( 1997) ISSN: 1059-7794 [Print] United States
PMID	9259198 (Publication Type: Journal Article)
Chemical References	Drosophila Proteins MAS1 protein, human Proto-Oncogene Mas Proto-Oncogene Proteins Arginine Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases Ret protein, Drosophila Deoxyribonucleases, Type II Site-Specific GCGC-specific type II deoxyribonucleases
Topics	Arginine (genetics) Carcinoma, Medullary (genetics) Deoxyribonucleases, Type II Site-Specific (genetics) Drosophila Proteins Female Genomic Imprinting Haplotypes Hirschsprung Disease (genetics) Humans Infant Jews Male Morocco (ethnology) Multiple Endocrine Neoplasia (genetics) Mutation Pedigree Polymorphism, Single-Stranded Conformational Proto-Oncogene Mas Proto-Oncogene Proteins (genetics) Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases (genetics) Sex Ratio Thyroid Neoplasms (genetics)

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