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Review
. 2021 Apr 14;10(8):1682.
doi: 10.3390/jcm10081682.

Founder Effects in Hereditary Hemorrhagic Telangiectasia

Tamás Major  1 , Réka Gindele  2 , Gábor Balogh  2 , Péter Bárdossy  3 , Zsuzsanna Bereczky  2
Affiliations
Review

Founder Effects in Hereditary Hemorrhagic Telangiectasia

Tamás Major et al. J Clin Med. .

Abstract

A founder effect can result from the establishment of a new population by individuals from a larger population or bottleneck events. Certain alleles may be found at much higher frequencies because of genetic drift immediately after the founder event. We provide a systematic literature review of the sporadically reported founder effects in hereditary hemorrhagic telangiectasia (HHT). All publications from the ACVRL1, ENG and SMAD4 Mutation Databases and publications searched for terms "hereditary hemorrhagic telangiectasia" and "founder" in PubMed and Scopus, respectively, were extracted. Following duplicate removal, 141 publications were searched for the terms "founder" and "founding" and the etymon "ancest". Finally, 67 publications between 1992 and 2020 were reviewed. Founder effects were graded upon shared area of ancestry/residence, shared core haplotypes, genealogy and prevalence. Twenty-six ACVRL1 and 12 ENG variants with a potential founder effect were identified. The bigger the cluster of families with a founder mutation, the more remarkable is its influence to the populational ACVRL1/ENG ratio, affecting HHT phenotype. Being aware of founder effects might simplify the diagnosis of HHT by establishing local genetic algorithms. Families sharing a common core haplotype might serve as a basis to study potential second-hits in the etiology of HHT.

Keywords: founder effect; genealogy; germline mutation; haplotype; hereditary hemorrhagic telangiectasia; population genetics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The algorithm of the literature search for hereditary hemorrhagic telangiectasia (HHT) founder effects.
Figure 2
Figure 2
The grade II to IV founder variants in the exons and flanking intronic regions of ACVRL1. Pathogenic variants are indicated in bold. In the case of the c.200G>A and the c.1121G>A variants, two distinct flanking haplotypes were identified [25].
Figure 3
Figure 3
The grade II to IV founder variants in the exons and flanking intronic regions of ENG. Pathogenic variants are indicated in bold.
See this image and copyright information in PMC

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