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Marked yield of re‐evaluating phenotype and exome/target sequencing data in 33 individuals with intellectual disabilities
Author(s) -
Xiao Bing,
Qiu Wenjuan,
Ji Xing,
Liu Xiaoqing,
Huang Zhuo,
Liu Huili,
Fan Yanjie,
Xu Yan,
Liu Yu,
Yie Hui,
Wei Wei,
Yan Hui,
Gong Zhuwen,
Shen Lixiao,
Sun Yu
Publication year - 2018
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38542
Subject(s) - exome sequencing , intellectual disability , exome , dna sequencing , phenotype , computational biology , mendelian inheritance , annotation , genetics , medicine , biology , bioinformatics , gene
The diagnosis of intellectual disability/developmental delay (ID/DD) benefits from the clinical application of target/exome sequencing. The yield in Mendelian diseases varies from 25% to 68%. The aim of the present study was to identify the genetic causes of 33 ID/DD patients using target/exome sequencing. Recent studies have demonstrated that reanalyzing undiagnosed exomes could yield additional diagnosis. Therefore, in addition to the normal data analysis, in this study, re‐evaluation was performed prior to manuscript preparation after updating OMIM annotations, calling copy number variations (CNVs) and reviewing the current literature. Molecular diagnosis was obtained for 19/33 patients in the first round of analysis. Notably, five patients were diagnosed during the re‐evaluation of the geno/phenotypic data. This study confirmed the utility of exome sequencing in the diagnosis of ID/DD. Furthermore, re‐evaluation leads to a 15% improvement in diagnostic yield. Thus, to maximize the diagnostic yield of next‐generation sequencing (NGS), periodical re‐evaluation of the geno/phenotypic data of undiagnosed individuals is recommended by updating the OMIM annotation, applying new algorithms, reviewing the literature, sharing pheno/genotypic data, and re‐contacting patients.