Journal
FRONTIERS IN GENETICS
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fgene.2018.00594
Keywords
autism spectrum disorder; whole exome sequencing; diagnostic yield; comorbidity; genetic etiology
Categories
Funding
- Shanghai Municipal Commission of Health and Family Planning [2017ZZ02026, 2018BR33, 2017EKHWYX-02, GDEK201709, 201740192]
- Shanghai Shenkang Hospital Development Center [16CR2025B]
- Shanghai Municipal Education Commission [20152234]
- National Natural Science Foundation of China [81571031, 81761128035, 81670812]
- Shanghai Committee of Science and Technology [17XD1403200, 18DZ2313505]
- Xinhua Hospital of Shanghai Jiao Tong University School of Medicine [2018YJRC03, 014, 201603]
- Jiao Tong University Cross Biomedical Engineering [YG2017MS72]
- Shanghai Shen Kang Hospital Development Center new frontier technology joint project [SHDC12017109]
- Youth Research Project of the Shanghai Municipal Health and Family Planning Commission [20184Y0348]
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Autism spectrum disorder (ASD) is a group of clinically and genetically heterogeneous neurodevelopmental disorders. Recent tremendous advances in the whole exome sequencing (WES) enable rapid identification of variants associated with ASD including single nucleotide variations (SNVs) and indels. To further explore genetic etiology of ASD in Chinese children with negative findings of copy number variants (CNVs), we applied WES in 80 simplex families with a single affected offspring with ASD or suspected ASD, and validated variations predicted to be damaging by Sanger sequencing. The results showed that an overall diagnostic yield of 8.8% (9.2% in the group of ASD and 6.7% in the group of suspected ASD) was observed in our cohort. Among patients with diagnosed ASD, developmental delay or intellectual disability (DD/ID) was the most common comorbidity with a diagnostic yield of 13.3%, followed by seizures (50.0%) and craniofacial anomalies (40.0%). All of identified de novo SNVs and indels among patients with ASD were loss of function (LOF) variations and were slightly more frequent among female (male vs. female: 7.3% vs. 8.5%). A total of seven presumed causative genes (CHD8, AFF2, ADNP, POGZ, SHANKS, IL1RAPL1, and PTEN) were identified in this study. In conclusion, WES is an efficient diagnostic tool for diagnosed ASD especially those with negative findings of CNVs and other neurological disorders in clinical practice, enabling early identification of disease related genes and contributing to precision and personalized medicine.
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