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Thyroid. 2017 Dec;27(12):1505-1510. doi: 10.1089/thy.2017.0404. Epub 2017 Nov 3.

Founder Effect of the RETC611Y Mutation in Multiple Endocrine Neoplasia 2A in Denmark: A Nationwide Study.

Author information

1
1 Department of ORL Head and Neck Surgery, Odense University Hospital , Odense, Denmark .
2
2 Department of Clinical Research, University of Southern Denmark , Odense, Denmark .
3
3 Department of Clinical Medicine and Endocrinology, Aalborg University Hospital , Aalborg, Denmark .
4
4 Department of Internal Medicine and Endocrinology, Aarhus University Hospital , Aarhus, Denmark .
5
5 Department of Medical Endocrinology, Copenhagen University Hospital , Copenhagen, Denmark .
6
6 Department of Molecular Medicine, Aarhus University Hospital , Aarhus, Denmark .
7
7 Center for Genomic Medicine, Copenhagen University Hospital , Copenhagen, Denmark .
8
8 Bioinformatics Center, Department of Biology, University of Copenhagen , Copenhagen, Denmark .
9
9 Department of Clinical Genetics, Odense University Hospital , Odense, Denmark .

Abstract

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.

KEYWORDS:

C611Y; Cys611Tyr; Denmark; REarranged during Transfection (RET); founder effect; multiple endocrine neoplasia 2A (MEN2A)

PMID:
29020875
DOI:
10.1089/thy.2017.0404
[Indexed for MEDLINE]

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