M. Seri et al., A CYS634GLY SUBSTITUTION OF THE RET PROTOONCOGENE IN A FAMILY WITH RECURRENCE OF MULTIPLE ENDOCRINE NEOPLASIA TYPE 2A AND CUTANEOUS LICHEN AMYLOIDOSIS, Clinical genetics, 51(2), 1997, pp. 86-90
Germ-line mutations of the RET proto-oncogene, involving five cysteine
residues at codons 609, 611, 618, 620 and 634, are associated with tw
o variants of the inherited cancer syndrome multiple endocrine neoplas
ia type 2: type 2A and familial medullary thyroid carcinoma. The assoc
iation of multiple endocrine neoplasia type 2A with the dermatological
disorder cutaneous lichen amyloidosis has already been reported, and
mutations in the Cys634 have been identified in different families. We
describe here an additional pedigree in which multiple endocrine neop
lasia type 2A and cutaneous lichen amyloidosis cosegregate. A Cys634Gl
y was identified by direct sequencing of the RET proto-oncogene exon 1
1 in the affected individuals. The mutation creates a new HaeIII site,
and restriction analysis performed on all family members rules out th
e presence of the altered allele in two children and consequently the
risk of developing thyroid tumors. These results emphasize the role of
molecular analysis of the RET proto-oncogene in diagnosing presymptom
atically those individuals at risk of inheriting the disease allele.