A novel Czech kindred with familial medullary thyroid carcinoma and Hirschsprung's disease.
OBJECTIVE
The RET proto-oncogene is involved in neural crest disorders. Activating germline mutations in the RET proto-oncogene cause the development of familial medullary thyroid carcinoma (FMTC) or medullary thyroid carcinoma (MTC) as a part of multiple endocrine neoplasia type 2 (MEN2) syndrome. Inactivating germline mutations in the RET proto-oncogene are detected in Hirschsprung's disease (HSCR). Only in a very small number of families are these 2 diseases expressed together.


METHODS
This study presents a novel Czech kindred with FMTC-HSCR phenotype. Two family members (mother and daughter) were tested for RET germline mutations in exons 10, 11, 13, 14, 15, and 16.


RESULTS
Direct fluorescent sequencing of genomic DNA revealed a heterozygous mutation in the RET proto-oncogene in exon 10 at codon C609Y in both persons tested. This family was reclassified, thanks to genetic screening from the apparently sporadic MTC-HSCR to FMTC-HSCR.


CONCLUSIONS
The germline mutation was detected because of the systematic genetic screening of the RET proto-oncogene, which is useful for genetic counseling of potential risk of HSCR and MTC in other family members. This family could be added to the small worldwide cohort of families with MEN2A/FMTC-HSCR.
Dvoráková
Sárka
S
Department of Molecular Endocrinology, Institute of Endocrinology, Prague 11694, Czech Republic. sarka@obloha.cz
Dvoráková
Katerina
K
Malíková
Marcela
M
Skába
Richard
R
Vlcek
Petr
P
Bendlová
Bela
B
D000328:Adult; D018153:Czech Republic; D004247:DNA / Q000032:analysis; D005091:Exons; D005260:Female; D018095:Germ-Line Mutation; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008934:Mitogens; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D018299:Neoplasms, Ductal, Lobular, and Medullary / Q000235:genetics*; D010375:Pedigree; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
C000715470:MAS1 protein, human; D008934:Mitogens; D000090063:Proto-Oncogene Mas; D004247:DNA; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human