Clinical exome sequencing as the first-tier test for diagnosing developmental disorders covering both CNV and SNV: a Chinese cohort

摘要: Background Developmental disorders (DDs) are early onset affecting 5%–10% of children worldwide. Chromosomal microarray analysis detecting CNVs is currently recommended as the first-tier test for DD diagnosis. However, this omits a high percentage disease-causing single nucleotide variations (SNVs) that warrant further sequencing. Currently, next-generation sequencing can be used in clinical scenarios CNVs, and use exome cohort ahead has not been evaluated. Methods Clinical (CES) was performed on 1090 unrelated Chinese patients who were classified into five phenotype subgroups. SNVs both detected analysed based data. Results An overall diagnostic rate 41.38% achieved with combinational CNV SNV. Over 12.02% diagnosed CNV, which comparable published CMA rate, while 0.74% traditionally elusive cases had dual diagnosis or apparently homozygous mutations clarified. The rates among subgroups ranged from 21.82% to 50.32%. top three recurrent cytobands 15q11.2-q13.1, 22q11.21 7q11.23. genes were: MECP2, SCN1A SCN2A. Both spectrums showed differences Conclusion With higher more comprehensive observation lower cost compared conventional strategies, simultaneous CES potential new choice diagnose DD.