Founder effect of the RET C611Y mutation in multiple endocrine neoplasia 2A in Denmark:A nationwide study
| Autor: | Jens Peter Kroustrup, Jes Sloth Mathiesen, Anja Lisbeth Frederiksen, Åse Krogh Rasmussen, Per Løgstrup Poulsen, Ulla Feldt-Rasmussen, Anders Albrechtsen, Finn Cilius Nielsen, Kim Brixen, Christian Godballe, Mette Gaustadnes, Kirstine Stochholm, Torben F. Ørntoft, Maria Rossing, Peter Vestergaard |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Genotype
Endocrinology Diabetes and Metabolism Denmark 030209 endocrinology & metabolism Biology medicine.disease_cause Identity by descent Polymorphism Single Nucleotide 03 medical and health sciences Multiple Endocrine Neoplasia Type 2a/genetics 0302 clinical medicine Endocrinology Germline mutation Gene Frequency medicine Journal Article Humans Multiple endocrine neoplasia multiple endocrine neoplasia 2A (MEN2A) Allele frequency Germ-Line Mutation Genetics Mutation REarranged during Transfection (RET) Haplotype C611Y Exons Proto-Oncogene Proteins c-ret/genetics medicine.disease Cys611Tyr Founder Effect Pedigree 030220 oncology & carcinogenesis Thyroid Neoplasms/genetics Founder effect |
| Zdroj: | Mathiesen, J S, Kroustrup, J P, Vestergaard, P, Stochholm, K, Poulsen, P L, Rasmussen, Å K, Feldt-Rasmussen, U, Gaustadnes, M, Ørntoft, T F, Rossing, M, Nielsen, F C, Albrechtsen, A, Brixen, K, Godballe, C & Frederiksen, A L 2017, ' Founder effect of the RET C611Y mutation in multiple endocrine neoplasia 2A in Denmark : A nationwide study ', Thyroid, vol. 27, no. 12, pp. 1505-1510 . https://doi.org/10.1089/thy.2017.0404 Mathiesen, J S, Kroustrup, J P, Vestergaard, P, Stochholm, K, Poulsen, P L, Rasmussen, Å K, Feldt-Rasmussen, U, Gaustadnes, M, Ørntoft, T F, Rossing, M, Nielsen, F C, Albrechtsen, A, Brixen, K, Godballe, C & Frederiksen, A L 2017, ' Founder effect of the RET C611Y mutation in multiple endocrine neoplasia 2A in Denmark: A nationwide study ', Thyroid : official journal of the American Thyroid Association, vol. 27, no. 12, pp. 1505-1510 . https://doi.org/10.1089/thy.2017.0404 |
| DOI: | 10.1089/thy.2017.0404 |
| Popis: | Background: Multiple endocrine neoplasia (MEN) 2A and 2B are caused by REarranged during Transfection (RET) germline mutations. In a recent nationwide study, an unusually high prevalence (33%) of families with the C611Y mutation was reported, and it was hypothesized that this might be due to a founder effect. The first nationwide study of haplotypes in MEN2A families was conducted, with the aim of investigating the relatedness and occurrence of de novo mutations among Danish families carrying similar mutations. Methods: The study included 21 apparently unrelated MEN2A families identified from a nationwide Danish RET cohort from 1994 to 2014. Twelve, two, two, three, and two families carried the C611Y, C618F, C618Y, C620R, and C634R mutations, respectively. Single nucleotide polymorphism chip data and identity by descent analysis were used to assess relatedness. Results: A common founder mutation was found among all 12 C611Y families and between both C618Y families. No relatedness was identified in the remaining families. Conclusion: The data suggest that all families with the C611Y germline mutation in Denmark originate from a recent common ancestor, probably explaining the unusually high prevalence of this mutation. Additionally, the results indicate that the C611Y mutation rarely arises de novo, thus underlining the need for thorough multigenerational genetic work up in carriers of this mutation. |
| Databáze: | OpenAIRE |
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