One in every 777 pregnant women in Taiwan carries a premutation in the FMR1 gene, which is associated with a greater likelihood of having a child with fragile X syndrome, a large study reports.
This is a higher-than-anticipated prevalence, although lower than Western populations, the scientists noted.
The research, “Fragile X syndrome carrier screening in pregnant women in Chinese Han population,” was published in the journal Scientific Reports.
Fragile X, the most frequent genetic cause of autism, is caused by the expansion of CGG repeats in the FMR1 gene, which provides instructions for making the fragile X mental retardation protein, or FMRP. Of note, C stands for cytosine and G for guanine, two of the four building blocks of DNA.
“Full” mutation carriers typically have more than 200 CGG repeats, while premutation carriers have between 55 and 200 of such repeats.
While premutation carriers can have normal FMR1 activity, their children are at a higher risk for acquiring the full mutation. In addition, premutation carriers can develop FMR1-related disorders in their adult life, including fragile X-associated tremor-ataxia syndrome.
The prevalence of fragile X in the Chinese population has been regarded as low, which puts into question the need to conduct screenings. Yet, recent studies in populations from Hong Kong and Korea indicate that approximately one out of 883 parents carry FMR1 gene mutations.
Researchers assessed the actual prevalence of premutation and full mutation carriers among 20,188 pregnant Taiwanese women of Han Chinese ethnicity who underwent genetic testing. Average age was 31.7 years, and age range was 20 to 54. Those who tested positive were referred for genetic counselling.
“This is by far the largest study of the reproductive FXS carrier screening in Chinese women,” the team wrote.
Results showed that 19,982 women (98.9%) had less than 45 CGG repeats and were considered normal. Nearly 40% of women (39.3%) carried 29 CGG repeats, followed by 25.6% with 30 repeats. Less than 10% had 28 (8.60%) and 36 repeats (6%).
A total of 26 women (0.13%, or one in 777) were carriers of FMR1 premutations. Twenty-one women underwent amniocentesis to assess genetic disorders of the fetus, while five women underwent genetic tests after delivery.
Premutations were passed from mother to fetus in 17 pregnancies, with six expanding to full mutations. All 11 fetuses carrying premutations were delivered, while four out of six pregnancies with full mutations were terminated.
One mother had an asymptomatic full mutation with 280 CGG repeats. She had a family history of intellectual disability and terminated a first pregnancy of a male fetus carrying a FMR1 gene deletion. Unlike females, males have only one X chromosome so a full mutation in the only FMR1 gene copy (allele) means that they will develop fragile X. After genetic counselling, the woman experienced a successful second pregnancy and gave birth to a girl.
A rarer genetic alteration was found in one woman, who had 29 CGG repeats in one allele and a DNA deletion with nine CGG repeats in the other FMR1 allele. She decided to terminate her pregnancy of a male fetus who would have inherited this deletion.
Researchers also conducted a cost analysis of this large genetic screening. A test to identify premutation and full mutation carriers cost around $118,885 US. The total cost of amniocentesis (about $100 US per procedure) and prenatal fragile X genetic testing to identify a fetus with a full mutation is approximately $410,091 US.
“Our research results also show that FXS [fragile X] carriers are not at all rare in Chinese,” but they are much more rare than in western countries, the researchers wrote.
“The reported FXS carrier rate in Taiwan is important for prenatal counseling and for the implementation of universal screening as a public health policy,” they added.