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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1994 Dec;55(6):1076–1082.

Parent-of-origin effects in multiple endocrine neoplasia type 2B.

K M Carlson 1, J Bracamontes 1, C E Jackson 1, R Clark 1, A Lacroix 1, S A Wells Jr 1, P J Goodfellow 1
PMCID: PMC1918453  PMID: 7977365

Abstract

Multiple endocrine neoplasia type 2B (MEN 2B) is characterized by medullary thyroid carcinoma, pheochromocytomas, mucosal neuromas, ganglioneuromas, and skeletal and ophthalmic abnormalities. It is observed as both inherited and sporadic disease, with an estimated 50% of cases arising de novo. A single point mutation in the catalytic core region of the receptor tyrosine kinase, RET, has been observed in germ-line DNA of MEN 2B patients. We have analyzed 25 cases of de novo disease in order to determine the parental origin of the mutated RET allele. In all cases the new mutation was of paternal origin. We observe a distortion of the sex ratio in both de novo MEN 2B patients and the affected offspring of MEN 2B transmitting males. These results suggests a differential susceptibility of RET to mutation in paternally and maternally derived DNA and a possible role for imprinting of RET during development.

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Selected References

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