Zhang Wen, Li Dong, Pang Nan, Jiang Li, Li Baomin, Ye Fanghua, He Fang, Chen Shimeng, Liu Fangyun, Peng Jing, Yin Jinghua, Yin Fei
Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China.
Hunan Intellectual and Developmental Disabilities Research Center, Pediatrics, Changsha, China.
Front Pediatr. 2022 Jul 22;10:911805. doi: 10.3389/fped.2022.911805. eCollection 2022.
Although 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.
In 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 ( = 681) from three hospitals.
Of 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).
This 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.
尽管许多不明原因的智力残疾/全面发育迟缓（ID/GDD）个体受益于拷贝数变异检测和下一代测序检测的高检出率，但仍有许多个体患有病因不明的ID/GDD。在本研究中，我们调查了脆性X综合征（FXS）检测在基因检测为阴性或未进行基因检测的不明原因ID/GDD个体中的适用性。
在本研究中，我们使用三联体重复引物聚合酶链反应来评估FXS检测在来自三家医院基因检测为阴性或未进行基因检测的不明原因ID/GDD个体（n = 681）中的价值和应用。
在通过FXS检测发现基因检测结果为阴性或未进行基因检测的681例ID/GDD个体中，12名男性和1名女性呈阳性。这相当于我们队列中FXS检测的诊断率为1.9%。所有FXS个体均有ID/GDD家族史或提示性临床特征。在完成基因检测的ID/GDD个体中FXS检测的检出率（2.70%，12/438）显著高于未进行任何基因检测的个体（0.40%，1/243）。
这是首次关于对之前未进行基因检测的ID/GDD个体进行FXS检测的报告，这促进了FXS诊断过程的标准化。这些结果突出了对标准基因检测结果为阴性的不明原因ID/GDD个体进行FXS检测的效用。在下一代测序时代，FXS检测更适合作为二线选择，并为临床医生和遗传学家追踪ID/GDD的病因提供辅助参考。
