ICNC Abstracts, ICNC 2018

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Reanalysis of the whole exome sequencing raw data and the clinical information can yield additional diagnosis missed by previously commercial genetic test report in children with epilepsy and intellectual disability
Jinliang Li, Kai Gao, Yuwu Jiang

Last modified: 2018-09-09

Abstract


Purpose: To evaluate whether reanalysis of the whole exome sequencing (WES) raw data and the clinical information can yield additional diagnosis in patients with negative commercial genetic test report, and to explore the reason of the false-negative result.

Methods: We reanalyzed the WES raw data and the clinical information of 37 families whose commercial genetic test report was negative previously. If the reanalysis result is positive, we explore the reason for their false-negative report.

Results: Four patients (11%, 4/37) were found the real diagnose after reanalysis. The first case was caused by a de novo mutation in HDAC8 and got a definitive diagnosis of Cornelia de Lange syndrome. The reason for the previous false negative was the patient's phenotype wasn’t exactly and completely collected. The second case was caused by a de novo mutation in CAMK2A. The initial report of the case was in May 2017, but the paper that linked CAMK2A to Mental Retardation was published in Nov 2017. The third case had biallelic mutation in HIBCH which associated to 3-hyroxyisobutyryl-CoA hydrolase deficiency. One of his mutations was considered as non-pathogenic because mistaken as synonymous at the time of initial analysis, but we found that it can affect splicing. The fourth case had biallelic mutation in PRUNE1 which associated to neurodevelopmental disorder. The initial report of this case was in Apr 2016 and the first paper about PRUNE1 related disease was published in Nov 2017.

Conclusions: To maximize the diagnostic yield of WES, reanalysis was necessary and important.


Keywords


whole exome sequencing; reanalysis; diagnostic yield

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