A Cys634Gly substitution of the RET proto-oncogene in a family with recurrence of multiple endocrine neoplasia type 2A and cutaneous lichen amyloidosis.
Germ-line mutations of the RET proto-oncogene, involving five cysteine residues at codons 609, 611, 618, 620 and 634, are associated with two variants of the inherited cancer syndrome multiple endocrine neoplasia type 2: type 2A and familial medullary thyroid carcinoma. The association 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 neoplasia type 2A and cutaneous lichen amyloidosis cosegregate. A Cys634Gly was identified by direct sequencing of the RET proto-oncogene exon 11 in the affected individuals. The mutation creates a new HaeIII site, and restriction analysis performed on all family members rules out the 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 presymptomatically those individuals at risk of inheriting the disease allele.
Seri
M
M
Laboratorio Genetica Moleculare, Istituto G. Gaslini, Genova Quarto, Italy.
Celli
I
I
Betsos
N
N
Claudiani
F
F
Camera
G
G
Romeo
G
G
D000293:Adolescent; D000328:Adult; D000686:Amyloidosis / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D003545:Cysteine / Q000235:genetics; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D005260:Female; D005998:Glycine / Q000235:genetics; D006801:Humans; D017512:Lichenoid Eruptions / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA
D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; D015252:Deoxyribonucleases, Type II Site-Specific; C024403:GGCC-specific type II deoxyribonucleases; D003545:Cysteine; D005998:Glycine