Development of Chinese genetic reference panel for Fragile X Syndrome and its application to the screen of 10,000 Chinese pregnant women and women planning pregnancy

BACKGROUND: Fragile X syndrome (FXS) is the most common inherited form of intellectual disability caused by a CGG repeat expansion in the 5′ untranslated region of the FMR1 gene. When the number of repeats exceeds 200, the gene becomes hypermethylated and is transcriptionally silenced, resulting in FXS. Other allelic forms of the gene that are studied because of their instability or phenotypic consequence include intermediate alleles (45–54 CGG repeats) and premutation alleles (55–200 repeats). Normal alleles are classified as having <45 CGG repeats. Population screening studies have been conducted among American and Australian populations; however, large population‐based studies have not been completed in China. METHODS AND RESULTS: In this work we present FXS screening results from 10,145 women of childbearing age from China. We first created and tested a standard panel that was comprised of normal, intermediate, premutation, and full mutation samples, and we performed the screening after confirming the consistency of genotyping results among laboratories. CONCLUSION: Based on our findings, we have determined the intermediate and premutation carrier prevalence of 1/130 and 1/634, respectively, among Chinese women.