The second-tier status of fragile X syndrome testing for unexplained intellectual disability/global developmental delay in the era of next-generation sequencing

Wen Zhang; Wen Zhang; Wen Zhang; Dong Li; Dong Li; Dong Li; Nan Pang; Nan Pang; Nan Pang; Li Jiang; Baomin Li; Fanghua Ye; Fang He; Fang He; Fang He; Shimeng Chen; Shimeng Chen; Shimeng Chen; Fangyun Liu; Fangyun Liu; Fangyun Liu; Jing Peng; Jing Peng; Jing Peng; Jinghua Yin; Fei Yin; Fei Yin; Fei Yin

doi:10.3389/fped.2022.911805

Frontiers in Pediatrics (Jul 2022)

The second-tier status of fragile X syndrome testing for unexplained intellectual disability/global developmental delay in the era of next-generation sequencing

Wen Zhang,
Wen Zhang,
Wen Zhang,
Dong Li,
Dong Li,
Dong Li,
Nan Pang,
Nan Pang,
Nan Pang,
Li Jiang,
Baomin Li,
Fanghua Ye,
Fang He,
Fang He,
Fang He,
Shimeng Chen,
Shimeng Chen,
Shimeng Chen,
Fangyun Liu,
Fangyun Liu,
Fangyun Liu,
Jing Peng,
Jing Peng,
Jing Peng,
Jinghua Yin,
Fei Yin,
Fei Yin,
Fei Yin

Affiliations

Wen Zhang: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China
Wen Zhang: Hunan Intellectual and Developmental Disabilities Research Center, Pediatrics, Changsha, China
Wen Zhang: Clinical Research Center for Children Neurodevelopmental Disabilities of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
Dong Li: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China
Dong Li: Hunan Intellectual and Developmental Disabilities Research Center, Pediatrics, Changsha, China
Dong Li: Clinical Research Center for Children Neurodevelopmental Disabilities of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
Nan Pang: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China
Nan Pang: Hunan Intellectual and Developmental Disabilities Research Center, Pediatrics, Changsha, China
Nan Pang: Clinical Research Center for Children Neurodevelopmental Disabilities of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
Li Jiang: Department of Neurology, Children's Hospital Affiliated to Chongqing Medical University, Chongqing, China
Baomin Li: Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
Fanghua Ye: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China
Fang He: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China
Fang He: Hunan Intellectual and Developmental Disabilities Research Center, Pediatrics, Changsha, China
Fang He: Clinical Research Center for Children Neurodevelopmental Disabilities of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
Shimeng Chen: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China
Shimeng Chen: Hunan Intellectual and Developmental Disabilities Research Center, Pediatrics, Changsha, China
Shimeng Chen: Clinical Research Center for Children Neurodevelopmental Disabilities of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
Fangyun Liu: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China
Fangyun Liu: Hunan Intellectual and Developmental Disabilities Research Center, Pediatrics, Changsha, China
Fangyun Liu: Clinical Research Center for Children Neurodevelopmental Disabilities of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
Jing Peng: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China
Jing Peng: Hunan Intellectual and Developmental Disabilities Research Center, Pediatrics, Changsha, China
Jing Peng: Clinical Research Center for Children Neurodevelopmental Disabilities of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
Jinghua Yin: Department of Pathophysiology, Xiangya Hospital, Central South University, Changsha, China
Fei Yin: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China
Fei Yin: Hunan Intellectual and Developmental Disabilities Research Center, Pediatrics, Changsha, China
Fei Yin: Clinical Research Center for Children Neurodevelopmental Disabilities of Hunan Province, Xiangya Hospital, Central South University, Changsha, China

DOI: https://doi.org/10.3389/fped.2022.911805
Journal volume & issue: Vol. 10

Abstract

Read online

ObjectiveAlthough many unexplained intellectual disability/global developmental delay (ID/GDD) individuals have benefited from the excellent detection yield of copy number variations and next-generation sequencing testing, many individuals still who suffer from ID/GDD of unexplained etiology. In this study, we investigated the applicability of fragile X syndrome (FXS) testing in unexplained ID/GDD individuals with negative or absent genetic testing.MethodsIn this study, we used the triplet repeat primed polymerase chain reaction to evaluate the value and application of fragile X testing in unexplained ID/GDD individuals with negative or absent genetic testing (n = 681) from three hospitals.ResultsOf the 681 ID/GDD individuals with negative or absent genetic testing results detected by FXS testing, 12 men and one woman were positive. This corresponded to a diagnostic yield of 1.9% for FXS testing in our cohort. All FXS individuals had either a family history of ID/GDD or suggestive clinical features. The detection yield of FXS testing in ID/GDD individuals who completed genetic testing (2.70%, 12/438) was significantly higher than in individuals without any genetic testing (0.40%, 1/243).ConclusionsThis is the first report of FXS testing in ID/GDD individuals who lacked previous genetic testing, which promotes standardization of the FXS diagnostic process. These results highlight the utility of FXS testing of unexplained ID/GDD individuals with negative results from standard genetic testing. In the era of next-generation sequencing, FXS testing is more suitable as a second-tier choice and provides clinicians and geneticists with auxiliary references for tracing the etiology of ID/GDD.

Published in Frontiers in Pediatrics

ISSN: 2296-2360 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Pediatrics
Website: http://journal.frontiersin.org/journal/pediatrics

About the journal

Abstract

Keywords