Preclinical detection of men 2A gene carrier using linked DNA markers

Abstract

SummaryWe have performed preclinical risk estimation of multiple endocrine neoplasia type 2A (MEN 2A) by using the polymorphic DNA markers tightly linked to the MEN2A locus. The gene for MEN 2A has been assigned to the pericentromeric region of chromosome 10 by linkage analysis. The preclinical detection of gene carriers in MEN 2A families using tightly linked DNA markers is useful for surgical treatment at an early stage. The DNA markers, RBP3 (retinol-binding protein 3, interstitial) and FNRB (fibronectin receptor, beta polypeptide), are both tightly linked to the MEN2A locus, and are localized to opposite sides of the MEN2A locus. We have used RBP3 and FNRB as markers for preclinical diagnosis. Of 18 Japanese families with MEN 2A, 6 families are informative for both loci, and other 10 families are informative for either RBP3 or FNRB. In one informative family, a 20-year-old female is predicted to be the gene carrier (probability; about 99 ~o). She should be carefully followed up till full penetrance age. We conclude that DNAbased prediction of MEN 2A is an effective procedure for clinical use.

Medullary Thyroid Carcinoma: Recent Advances and Management Update

“…Thus currently it is not possible to be totally reliant on calcitonin values measured either by RIA or IRMA to discriminate RET mutation carriers from noncarriers or individuals with MTC or CCH from normals. If direct detection of germline mutations is not possible then standard linkage analysis with highly polymorphic tightly linked markers should be performed (110)(111)(112)(113). This type of analysis will give the individual a risk estimation of greater than 99% of inheriting the disease, assuming flanking markers are used.…”