Reanalysis of exome sequencing data of intellectual disability samples: Yields and benefits

被引：56

作者：

Al-Nabhani, Maryam ^{[1
]}

Al-Rashdi, Samiya ^{[1
]}

Al-Murshedi, Fathiya ^{[1
,2
]}

Al-Kindi, Adila ^{[1
,2
]}

Al-Thihli, Khalid ^{[1
,2
]}

Al-Saegh, Abeer ^{[1
,2
]}

Al-Futaisi, Amna ^{[3
]}

Al-Mamari, Watfa ^{[2
,3
]}

Zadjali, Fahad ^{[4
]}

Al-Maawali, Almundher ^{[1
,2
]}

机构：

[1] Sultan Qaboos Univ, Dept Genet, Coll Med & Hlth Sci, POB 35, Muscat 123, Oman

[2] Sultan Qaboos Univ Hosp, Genet & Dev Med Clin, Muscat, Oman

[3] Sultan Qaboos Univ, Dept Child Hlth, Coll Med & Hlth Sci, Muscat, Oman

[4] Sultan Qaboos Univ, Dept Biochem, Coll Med & Hlth Sci, Muscat, Oman

来源：

CLINICAL GENETICS | 2018年 / 94卷 / 06期

关键词：

diagnostic yield; DNAH14; DRG1; ID; LIN7B; RIC3; SYCL2; variant interpretation; whole-exome sequencing; RNA-BINDING PROTEIN; POLYADENOSINE RNA; VARIANTS; DIAGNOSIS; DISEASE;

D O I：

10.1111/cge.13438

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Recently, with the advancement in next generation sequencing (NGS) along with the improvement of bioinformatics tools, whole exome sequencing (WES) has become the most efficient diagnostic test for patients with intellectual disability (ID). This study aims to estimate the yield of a reanalysis of ID negative exome cases after data reannotation. Total of 50 data files of exome sequencing, representing 50 samples were collected. The inclusion criteria include ID phenotype, and previous analysis indicated a negative result (no abnormality detected). These files were pre-processed and reannotated using ANNOVAR tool. Prioritized variants in the 50 cases studied were classified into three groups, (1) disease-causative variants (2) possible disease-causing variants and (3) variants in novel genes. Reanalysis resulted in the identification of pathogenic/likely pathogenic variants in six cases (12%). Thirteen cases (26%) were classified as having possible disease-causing variants. Candidate genes requiring future functional studies were detected in seven cases (14%). Improvement in bioinformatics tools, update in the genetic databases and literature, and patients' clinical phenotype update were the main reasons for identification of these variants in this study.

引用

页码：495 / 501

页数：7

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