Genetic analysis of RET, GFRα1 and GDNF genes in Spanish families with multiple endocrine neoplasia type 2A
✍ Scribed by Laura Gil; Marta Azañedo; Marina Pollán; Eva Cristobal; Begoña Arribas; Luis García-Albert; Alfredo García-Sáiz; María Luisa Maestro; Antonio Torres; Javier Menárguez; José M. Rojas
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- French
- Weight
- 112 KB
- Volume
- 99
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
Multiple endocrine neoplasia type 2A (MEN 2A) is associated with specific germline missense mutations in the RET proto‐oncogene. This locus encodes a receptor tyrosine kinase whose activation requires the formation of a multimeric receptor complex including GDNF as a ligand and GFRα1 as a coreceptor. In order to explore the role of RET, GFRα1 and GDNF genes in the variation of phenotypes observed in MEN2A families, we analysed germline mutations of these genes in 4 unrelated Spanish MEN2A families (23 cases studied). We found 2 novel variants corresponding to a single change in position + 47 (intron 12) of RET and position +22 (intron 7) of GFRα1. Furthermore, we observed strong co‐segregation between 2 polymorphisms of RET [G691S (exon 11) and S904S (TCC‐TCG, exon 15) (100%, Fisher's exact test, p< 0.001)]. More interestingly, we found that these polymorphisms occurred at a significantly high frequency in patients with age at onset < 20 years old (Kruskal‐Wallis's and Fisher's exact test, p = 0.007). These findings suggest that the G691S and S904S variants of RET may somehow play a role on the age of onset of MEN 2A. © 2002 Wiley‐Liss, Inc.