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

Xiaoli Chen,Wenjuan Zhou,Jian Qin,Xiru Wu,Ye Wu,Liwen Wang,Zhiming Xiong,Yu Zhang,Jin Guo,Yuwu Jiang,Jun Wang,Taoyun Ji,Gary J Latham,Qiang Gu,Jingmin Wang,Hua Xie,Xiaozhen Zhang

doi:10.1186/s12887-015-0394-8

Abstract

BackgroundFragile 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.MethodsPatients 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).Results553 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12887-015-0394-8) contains supplementary material, which is available to authorized users.

Highlights

Fragile X syndrome is the most common genetic disorder of intellectual developmental disorder/ mental retardation (IDD/MR)
FMR1 Region-specific CGG PCR and triplet repeat-primed (TP)–PCR produce concordant CGG sizing results that are in agreement with known genotypes We performed both the Region-specific CGG PCR and TP–PCR assay for seven samples with known CGG sizes
For samples with CGG repeats in the normal size range (13–43 CGG), single well-defined amplification bands were observed on a 2 % agarose gel (Fig. 1a)

Summary

Introduction

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. Intellectual developmental disorder/mental retardation (IDD/MR) encompasses a cluster of symptoms that are characterized by low intelligence and limitations in adaptive behavior and functional capabilities [1, 2]. IDD occurs in approximately 1-3 % of individuals worldwide, with an incidence of 1 % in high income countries and 2 % in low/middle income countries [3, 4]. Fragile X syndrome (FXS, MIM 309550) is the most common form of IDD. FXS accounts for approximately 20 % of patients with X-linked IDD [8] and 2–7 % of children with autism [9, 10]. The lack of a clear phenotype in young children can delay a definitive diagnosis, leading to a diagnostic “odyssey” for families and a

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