Background: Intellectual disability (ID) is a heterogeneous neurodevelopmental disorder with a complex genetic underpinning in its etiology. Chromosome microarray (CMA) is recommended as the first-tier diagnostic test for ID due to high detection rate of copy number variation (CNV). Methods: To identify an appropriate clinical detection scheme for ID in Han Chinese patients, whole genome low-coverage sequencing was performed as the first-tier diagnostic test, and medical exome sequencing (MES) as the second-tier diagnostic test for patients with negative results of CNVs.Results: A total of 19 pathogenic CNVs in 16/95(16.84%) ID patients and 10 pathogenic single-nucleotide variations (SNVs), including 6 novel mutations in 8/95(8.42%) ID patients were identified on whom no pathogenic CNVs were discovered. The detection rate of CNVs in ID with multiple congenital anomalies (MCA) subgroup was significantly higher than ID with autism spectrum disorders and other IDs subgroups. And the single-nucleotide variations showed a higher occurrence rate in the other IDs subgroup.Conclusions: There were differences in the diagnostic yields of different variation types among the three ID subgroups. Our findings provided a new perspective on appropriate clinical detection scheme in different ID subgroups based on statistically significant differences among the three ID subgroups. The application of whole genome low-coverage sequencing as the first-tier diagnostic test for ID with MCA subgroup and MES as the first-tier diagnostic test for other ID subgroup was considered as an efficient clinical detection scheme.
Background: Intellectual disability (ID) is a heterogeneous neurodevelopmental disorder with a complex genetic underpinning in its etiology. Chromosome microarray (CMA) is recommended as the first-tier diagnostic test for ID due to high detection rate of copy number variation (CNV). Methods: To identify an appropriate clinical detection scheme for ID in Han Chinese patients, a whole genome low-coverage sequencing was performed as the first-tier diagnostic test, followed by medical exome sequencing as the second-tier diagnostic test for those patients with negative results of CNVs. Results: A total of 19 pathogenic CNVs in 16/95(16.84%) ID patients and 11 pathogenic single-nucleotide variations, including 7 novel mutations in 9/79(11.39%) ID patients were identified on whom no pathogenic CNVs were discovered. The detection rate of ID CNVs in multiple congenital anomalies (MCA) subgroup was significantly higher than ID with autism spectrum disorder and the other IDs subgroup. Also single-nucleotide variations showed a higher occurrence rate in the other IDs subgroup. Conclusions: There were differences in the diagnostic yields of different variation types among the three ID subgroups. Our findings provided a new perspective on appropriate clinical detection scheme for different ID subgroups based on the statistical results of different ID subgroups. The application of whole genome low-coverage sequencing as the first-tier diagnostic test for ID with MCA subgroup and medical exome sequencing as the first-tier diagnostic test for other IDs subgroup were considered as an efficient clinical detection schemes.
Background: Intellectual disability (ID) is a heterogeneous neurodevelopmental disorder with a complex genetic underpinning in its etiology. Chromosome microarray (CMA) is recommended as the first-tier diagnostic test for ID due to high detection rate of copy number variation (CNV). Methods: To identify an appropriate clinical detection scheme for ID in Han Chinese patients, a whole genome low-coverage sequencing was performed as the first-tier diagnostic test, followed by medical exome sequencing as the second-tier diagnostic test for those patients with negative results of CNVs. Results: A total of 19 pathogenic CNVs in 16/95(16.84%) ID patients and 11 pathogenic single-nucleotide variations, including 7 novel mutations in 9/79(11.39%) ID patients were identified on whom no pathogenic CNVs were discovered. The detection rate of CNVs in ID s with multiple congenital anomalies (MCA) subgroup was significantly higher than ID s with autism spectrum disorder and the other IDs subgroup. Also single-nucleotide variations showed a higher occurrence rate in the other IDs subgroup. Conclusions: There were differences in the diagnostic yields of different variation types among the three ID subgroups. Our findings provided a new perspective on appropriate clinical detection scheme for different ID subgroups based on the statistical results of different ID subgroups. The application of whole genome low-coverage sequencing as the first-tier diagnostic test for ID with MCA subgroup and medical exome sequencing as the first-tier diagnostic test for other IDs subgroup were considered as an efficient clinical detection schemes.
Background: Intellectual disability (ID) is a heterogeneous neurodevelopmental disorder with a complex genetic underpinning in its etiology. Chromosome microarray (CMA) is recommended as the first-tier diagnostic test for ID due to high detection rate of copy number variation (CNV). Methods: To identify an appropriate clinical detection scheme for ID in Han Chinese patients, whole genome low-coverage sequencing was performed as the first-tier diagnostic test, and medical exome sequencing (MES) as the second-tier diagnostic test for patients with negative results of CNVs. Results: A total of 19 pathogenic CNVs in 16/95(16.84%) ID patients and 10 pathogenic single-nucleotide variations (SNVs), including 6 novel mutations in 8/95(8.42%) ID patients were identified on whom no pathogenic CNVs were discovered. The detection rate of CNVs in ID with multiple congenital anomalies (MCA) subgroup was significantly higher than ID with autism spectrum disorders and other IDs subgroups. And the single-nucleotide variations showed a higher occurrence rate in the other IDs subgroup. Conclusions: There were differences in the diagnostic yields of different variation types among the three ID subgroups. Our findings provided a new perspective on appropriate clinical detection scheme in different ID subgroups based on statistically significant differences among the three ID subgroups. The application of whole genome low-coverage sequencing as the first-tier diagnostic test for ID with MCA subgroup and MES as the first-tier diagnostic test for other ID subgroup was considered as an efficient clinical detection scheme.
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