Population-based FMR1 carrier screening among reproductive women

J Assist Reprod Genet. 2024 Nov;41(11):3237-3243. doi: 10.1007/s10815-024-03242-2. Epub 2024 Sep 25.

Abstract

Purpose: Fragile X syndrome (FXS) is a neurodevelopmental disorder, caused by an CGG repeat expansion (FM, > 200 CGG) in the fragile X messenger ribonucleoprotein 1 (FMR1) gene. Female carriers of a premutation (PM; 55-200 CGG) can transmit the PM allele, which, depending on the CGG allele size, can expand to an allele in the FM range in the offspring.

Methods: Carrier screening for FMR1 PM is not available in Thailand. This study aimed to investigate the prevalence of PM carriers among Thai reproductive women at the tertiary hospital. A total of 1250 females participated in this study; ages ranged from 20 to 45 years, mean of 30 years (S.D. = 6.27).

Results: Two carriers of a premutation allele, with 32,62 and 32,69 CGG repeats respectively, were identified. This corresponds to 1 in 600 women or 0.17% of the population. Further, three women carrying a gray zone allele (45-54 CGG repeats) were identified (29,51; 29,49; and 30,47 CGG repeats) which equals to 1:400 women or 0.25% of the population. No FM case was detected.

Conclusions: This study heightens the importance of PM carrier screening of women of reproductive age, particularly for the higher risk of developing fragile X-associated primary ovarian insufficiency (FXPOI). Early identification of PM carrier status enhances family planning and fecundity alternatives and improves reproductive health outcomes leading to a better life.

Keywords: Carrier screening; FXPAC; FXPOI; Premutation; Prevalence.

MeSH terms

  • Adult
  • Alleles*
  • Female
  • Fragile X Mental Retardation Protein* / genetics
  • Fragile X Syndrome* / diagnosis
  • Fragile X Syndrome* / epidemiology
  • Fragile X Syndrome* / genetics
  • Genetic Carrier Screening* / methods
  • Genetic Testing / methods
  • Heterozygote*
  • Humans
  • Middle Aged
  • Mutation / genetics
  • Primary Ovarian Insufficiency / epidemiology
  • Primary Ovarian Insufficiency / genetics
  • Primary Ovarian Insufficiency / pathology
  • Thailand / epidemiology
  • Trinucleotide Repeat Expansion* / genetics
  • Young Adult

Substances

  • Fragile X Mental Retardation Protein
  • FMR1 protein, human