[P2-11] Submicroscopic chromosomal aberrations as a major cause of developmental delay, intellectual disability and autism spectrum disorder
The majority of affected children with development delay (DD) also develop intellectual disability (ID). DD / ID affect about 3% in general population, while one in 500 individuals is affected with autism spectrum disorder (ASD). Up to date, the etiology of DD/ID and ASD is heterogeneous. Herein, we introduced cohort of Taiwanese of 50 children with DD/ID/ASD analyzed by array comparative genomic hybridization (aCGH) for identification of copy number variants (CNV).
Of the 50 patients, abnormal microarray results were seen in 30 individuals with a total of 47 CNVs. There are 20 chromosomes involved and aberration is most common found in chromosome X. Thirteen of the 50 patients have aberrations involved in two chromosomes, the remaining have one chromosome involved in each proband. Of the 47 CNVs, 16 are microduplications and 31 are microdeletions. The gender ratio (M:F) of microdeletions and microduplications is 2.2 and 2, respectively. The size of microduplication / microdeletion ranges from 0.010 Mb to 11.6 Mb, causing gene dosage imbalance from 1 gene to 124 genes. Fourteen genes are recognized as association with ASD and/or other neuropsychiatric disorders, or implicated in synaptic and neuronal activity. Three pathogenic CNVs contain imprinting genes contributing to epigenetic mechanism of diseases. Only two of the 6 probands with congenital anomalies have chromosomal aberrations.
In our cohort of DD/ID/ASD, aCGH offers a higher diagnostic yield of chromosomal aberration than the traditional G-banded karyotype, suggest aCGH as a promising first tier analysis for the detecting genomic rearrangements in individuals with DD/ID/ASD.
chromosomal imbalances and human disease, together with a broad clinical characterization of affected individuals, will be able to elucidate the genotype-phenotype correlations.
Of the 50 patients, abnormal microarray results were seen in 30 individuals with a total of 47 CNVs. There are 20 chromosomes involved and aberration is most common found in chromosome X. Thirteen of the 50 patients have aberrations involved in two chromosomes, the remaining have one chromosome involved in each proband. Of the 47 CNVs, 16 are microduplications and 31 are microdeletions. The gender ratio (M:F) of microdeletions and microduplications is 2.2 and 2, respectively. The size of microduplication / microdeletion ranges from 0.010 Mb to 11.6 Mb, causing gene dosage imbalance from 1 gene to 124 genes. Fourteen genes are recognized as association with ASD and/or other neuropsychiatric disorders, or implicated in synaptic and neuronal activity. Three pathogenic CNVs contain imprinting genes contributing to epigenetic mechanism of diseases. Only two of the 6 probands with congenital anomalies have chromosomal aberrations.
In our cohort of DD/ID/ASD, aCGH offers a higher diagnostic yield of chromosomal aberration than the traditional G-banded karyotype, suggest aCGH as a promising first tier analysis for the detecting genomic rearrangements in individuals with DD/ID/ASD.
chromosomal imbalances and human disease, together with a broad clinical characterization of affected individuals, will be able to elucidate the genotype-phenotype correlations.