Population-based Carrier Screening and Prenatal Diagnosis of Fragile X
Syndrome in East Asian Populations
Abstract
Identification of carriers of fragile X syndrome (FXS) with the
subsequent prenatal diagnosis, and knowledge of FXS-associated genetic
profiles are essential for intervention in specific populations. We
report the results of carrier screening of 39,458 East Asian adult women
and prenatal diagnosis from 87 FXS carriers. The prevalence of FXS
carriers and incidence of full mutation fetuses in carrier pregnancies
were found to be 1/556 and 11.0%, respectively. We confirmed the
validity of the current threshold of CGG repeats for FMR1
categorization; the integral risks of full mutation expansion were
approximately 6.0%, 43.8%, and 100% for premutation alleles with
55-74, 75-89, and ≥90 CGG repeats, respectively. The protective effect
of AGG interruption in East Asian populations was validated, which is
important in protecting premutation alleles with 75-89 CGG repeats from
full mutation expansion. Lastly, family history was shown not an
effective indicator for FXS carrier screening in East Asian populations
and population-based screening was more cost-effective. This study
provides an insight into the largest carrier screening and prenatal
diagnosis for FXS in East Asian populations to date. The FXS-associated
genetic profiles of East Asian populations are delineated and
population-based carrier screening is shown to be promising for FXS
intervention.