The genetics of recurrent hydatidiform moles in Mexico: further evidence of a strong founder effect for one mutation in NLRP7 and its widespread

J Assist Reprod Genet. 2021 Jul;38(7):1879-1886. doi: 10.1007/s10815-021-02132-1. Epub 2021 Mar 22.

Abstract

Purpose: To investigate the frequency of a founder mutation in NLRP7, L750V, in independent cohorts of Mexican patients with recurrent hydatidiform moles (RHMs).

Methods: Mutation analysis was performed by Sanger sequencing on DNA from 44 unrelated Mexican patients with RHMs and seven molar tissues from seven additional unrelated patients.

Results: L750V was present in homozygous or heterozygous state in 37 (86%) patients and was transmitted on the same haplotype to patients from different states of Mexico. We also identified a second founder mutation, c.2810+2T>G in eight (18.1%) patients, and a novel premature stop-codon mutation W653*.

Conclusion: Our data confirm the strong founder effect for L750V, which appears to be the most common mutation in NLRP7. We also report on six healthy live births to five patients with biallelic NLRP7 mutations, two from spontaneous conceptions and four from donated ovum and discuss our recommendations for DNA testing and genetic counseling.

Keywords: Founder mutation; Recurrent hydatidiform moles.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Female
  • Founder Effect*
  • Haplotypes
  • Heterozygote
  • Humans
  • Hydatidiform Mole / genetics*
  • Live Birth
  • Mexico
  • Mutation*
  • Polymorphism, Single Nucleotide
  • Pregnancy

Substances

  • Adaptor Proteins, Signal Transducing
  • NLRP7 protein, human