Fragile X syndrome screening in Chinese children with unknown intellectual developmental disorder
Xiaoli Chen1, Jingmin Wang2, Hua Xie3
1Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China. cxlwx@sina.com.
Insights
Fragile X syndrome (FXS) affects 0.93% of Chinese children with intellectual developmental disorder (IDD). A TP-PCR assay reliably identified FXS in this population, aiding clinical genetic diagnosis.
Area of Science:
- Genetics
- Developmental Biology
- Clinical Diagnostics
Background:
- Fragile X syndrome (FXS) is the most prevalent genetic cause of intellectual developmental disorder (IDD).
- The prevalence of FXS among Chinese children with IDD in mainland China remained unestablished prior to this study.
Purpose of the Study:
- To determine the prevalence of Fragile X syndrome (FXS) in Chinese children with unexplained moderate to severe intellectual developmental disorder (IDD).
- To evaluate the utility of a TP-PCR assay for identifying FXS in a clinical diagnostic setting.
Main Methods:
- Recruitment of 553 unrelated pediatric patients with unknown moderate to severe IDD from two children's hospitals.
- Utilized a commercial TP-PCR assay to determine the CGG repeat size in the FMR1 gene.
- Analyzed the influence of AGG interruptions on CGG expansion during maternal transmission in 24 mother-son pairs.
Main Results:
- High-quality TP-PCR data were obtained from 540 patients, with FMR1 CGG repeat numbers determined.
- Five full mutations (0.93% prevalence) were identified, including 1 familial and 4 sporadic cases of IDD.
- Size mosaicism was observed in 80% of identified FXS patients; AGG interruption patterns did not significantly impact CGG expansion during maternal transmission.
Conclusions:
- The FMR1 TP-PCR assay is a reliable, sensitive, and clinically suitable method for genetic diagnosis of FXS.
- The prevalence of FXS in Chinese children with unknown IDD is 0.93%.
Background:
Fragile X syndrome is the most common genetic disorder of intellectual developmental disorder/mental retardation (IDD/MR). The prevalence of FXS in a Chinese IDD children seeking diagnosis/treatment in mainland China is unknown.
Methods:
Patients with unknown moderate to severe IDD were recruited from two children's hospitals. Informed consent was obtained from the children's parents. The size of the CGG repeat was identified using a commercial TP-PCR assay. The influence of AGG interruptions on the CGG expansion during maternal transmission was analyzed in 24 mother-son pairs (10 pairs with 1 AGG and 14 pairs with 2 AGGs).
Results:
553 unrelated patients between six months and eighteen years of age were recruited. Specimens from 540 patients (male:female = 5.2:1) produced high-quality TP-PCR data, resulting in the determination of the FMR1 CGG repeat number for each. The most common repeat numbers were 29 and 30, and the most frequent interruption pattern was 2 or 3 AGGs. Five full mutations were identified (1 familial and 4 sporadic IDD patients), and size mosaicism was apparent in 4 of these FXS patients (4/5 = 80%). The overall yield of FXS in the IDD cohort was 0.93% (5/540). Neither the mean size of CGG expansion (0.20 vs. 0.79, p > 0.05) nor the frequency of CGG expansion (2/10 vs. 9/14, p > 0.05) was significantly different between the 1 and 2 AGG groups following maternal transmission.
Conclusions:
The FMR1 TP-PCR assay generates reliable and sensitive results across a large number of patient specimens, and is suitable for clinical genetic diagnosis. Using this assay, the prevalence of FXS was 0.93% in Chinese children with unknown IDD.
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