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Down syndrome and Fragile X syndrome are respectively the first and the second most common causes of congenital mental retardation. As the incidence of newborn Down syndrome has been successfully minimized by the effective prenatal screening and diagnosis, Fragile X syndrome has now become more important, affecting 1 in 4,000 to 10,000 males. The disease is caused by inheriting the abnormal gene from their carrier-mothers. The Department of Obstetrics and Gynaecology at The Chinese University of Hong Kong (CUHK) launches the territory’s first Fragile X carrier screening by introducing the new Fragile X PCR technology, which enable doctors to identify women with such hidden genetic problem.  

About 1 in 250-1000 females are asymptomatic carriers of the defected (pre-mutation) FMR1 gene located in the X chromosome, in which there is an increased number of unstable CGG trinucleotide repeat (55-200 times). Once this pre-mutation is transmitted to a male baby, there is a significant risk that the repeats will further expand to beyond 200 times (full-mutation), leading to mental disability and autism. Female carriers are also at risk of pre-mature menopause. Therefore, carrier screening may assist prenatal diagnosis of abnormal fetuses as well as assessment of women’s health. 

The traditional diagnostic method of Fragile X syndrome is Southern blot analysis. Although it is accurate in counting the number of CGG repeats, it is labour intensive and time-consuming and hence not suitable for large-scale screening purpose. The conventional PCR method allows rapid analysis but is incapable of counting repeats more than 130 times, resulting in false negative result. 

The Department of Obstetrics and Gynaecology of CUHK is the first to introduce Fragile X PCR, a new PCR method designed specifically for Fragile X mutation screening. Unlike the conventional PCR, it is capable of counting the CGG repeats up to 900 times, and can precisely distinguish normal (200 repeats). It is also a high throughput method and can produce results after one day. Recently, CUHK validated this new Fragile X PCR method on 14 full-mutation cases, 20 pre-mutation cases, and 75 normal controls with 100% accuracy. 

If a pregnant woman is confirmed to be a carrier, prenatal diagnosis can then be performed to check the fetus. CUHK has recently identified an affected male fetus of a carrier-mother using Fragile X PCR which assisted the management of her pregnancy. 

In conclusion, CUHK has successfully introduced a new technique —Fragile X PCR for carrier screening. The method overcomes the existing technical difficulties by providing rapid and accurate result. It is suitable for population-based screening as well as prenatal screening and diagnosis of Fragile X syndrome. For appointment or enquiry on the above service, please call 2632 6412.