Fragile X syndrome screening in Chinese children with unknown intellectual developmental disorder

BMC Pediatrics

Yuwu Jiang⁶  Gary J. Latham⁵  Xiru Wu⁶  Liwen Wang¹  Zhiming Xiong⁴  Yu Zhang¹  Taoyun Ji⁶  Xiaozhen Zhang²  Qiang Gu⁶  Jin Guo¹  Jian Qin⁷  Jun Wang³  Ye Wu⁶  Wenjuan Zhou⁶  Hua Xie¹  Jingmin Wang⁶  Xiaoli Chen¹ 

[1] Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China;Department of Genetics, Jiangxi Previncial Children’s Hospital, Jiangxi, China;Department of Neurology, Affiliated Children’s Hospital of Capital Institute of Pediatrics, Beijing, China;State Key Lab of Medical Genetics, Central South University, Changsha, China;Research & Technology Development, Asuragen, Inc., Austin, TX, USA;Department of Pediatrics, Peking University First Hospital, Beijing, China;Beijing Microread Genetech Co., Ltd, Beijing, China

关键词: Triplet repeat primed (TP)-PCR;    Fragile X syndrome;    FMR1;    Intellectual developmental disorder;    Chinese children;   

Others  :  1219313
DOI  :  10.1186/s12887-015-0394-8

 received in 2014-10-09, accepted in 2015-06-25,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Chen et al.

【 图 表 】

Fig. 1.

Fig. 2.

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