A rapid screen of the most common RET mutation associated with MEN 2A
- Childrens Hospital of Western Ontario (Canada)
- Victoria Hospital, Ontario (Canada)
Multiple endocrine neoplasia type 2A is a dominantly inherited condition predisposing the affected individual to the development of medullary thyroid carcinoma and phaeochromocytoma. This condition is associated with mutations within the coding sequence of the RET proto-oncogene, affecting specifically cysteine residues in the extracellular, ligand-binding domain of the RET gene product. A recent review reported that 13 of 28 mutations identified in the RET gene in individuals affected with MEN 2A involved a T{sub 1900}{r_arrow}C; Cys{sub 635}{r_arrow}Arg mutation. We report the results of molecular studies on two further local MEN 2A kindreds. Both of the RET exons 10 and 11 were initially screened, being amplified by PCR using leukocyte-derived DNA as template. They were either sequenced directly using a deaza dGTP sequencing protocol, or were cloned and sequenced using a TA vector. Affected individuals from both families carried the T{sub 1900}{r_arrow}C; Cys{sub 635}{r_arrow}Arg mutation. A newly created Hha I site was identified in the mutation allele. This allowed us to confirm the presence of the mutation, which was demonstrated to segregate with the clinical phenotype in both of these kindreds. Members of one of the affected kindreds were sampled by obtaining dried blood dots on Guthrie cards. These were used to prepare a lysate which served as the template for PCR amplification of exon 11, and allowed a diagnostic restriction enzyme digest with Hha I. It is noted furthermore that the Cys{sub 619}{r_arrow}Arg mutation, also reported previously, will similarly create a novel Hha I site. As these two mutations appear in as many as 50% of the cases of MEN 2A reported to date, it is suggested that Hha I be used in a preliminary screen for this disorder.
- OSTI ID:
- 134733
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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