Abstract
Chromosomal copy number variants (CNVs) are an important cause of congenital malformations and mental retardation. This study reported a large Chinese pedigree (4-generation, 76 members) with mental retardation caused by chromosome microduplication/microdeletion. There were 10 affected individuals with intellectual disability (ID), developmental delay (DD), and language delay phenotypes. SNP array analysis was performed in the proband and eight patients and found all of them had a microduplication of chromosome 4p16.3p15.2 and a microdeletion of chromosome 8p23.3p23.2. The high-resolution karyotyping analysis of the proband had unbalanced karyotype [46, XY, der(8)t(4;8)(p15.2;p23.1)mat], his mother had balanced karyotype [46, XX, t(4;8) (p15.2;p23.1)], whereas his father had normal karyotype [46,XY]. Fluorescence in situ hybridization (FISH) analysis further confirmed that the proband’s mother had a balanced translocation between the short arm terminal segment of chromosome 4 and the short arm end segment of chromosome 8, ish t(4;8)(8p + ,4q + ;4p + ,8q +). In conclusion, all the patients inherited chromosomes 8 with 4p16.3p15.2 duplication and 8p23.3p23.2 deletion from their parental balanced translocation, which might be the cause of the prevalence of intellectual disability. Meanwhile, 8p23.3p23.2 deletion, rather than 4p16.3p15.2 duplication might cause a more severe clinical syndrome.
Highlights
Intellectual disability (ID), referred as cognitive impairment or mental retardation, is characterized by a substantially below-average score on tests of mental ability or intelligence (intellectual quotient (IQ) < 70), and limitations in adaptive behaviors
We evaluated the copy number variations (CNVs) with the information provided by the Online Mendelian Inheritance in Man database (OMIM) [9], the in Humans using Ensembl Resources Database (DECIPHER) [10], the Database of Genomic Variants (DGV) [11], CHOP database [12] and literature
We detected that the chromosome aberration of the proband and other patients detected through Single nucleotide polymorphism (SNP) array were inherited from derived chromosome 8 [der(8)t(4;8)(p15.2;p23.1)] and normal chromosome 4 of balanced translocation carrier [t(4;8)(p15.2;p23.1)] in this intellectual family pedigree
Summary
Intellectual disability (ID), referred as cognitive impairment or mental retardation, is characterized by a substantially below-average score on tests of mental ability or intelligence (intellectual quotient (IQ) < 70), and limitations in adaptive behaviors. The etiology of ID is complex and can be the result of genetic and/or environmental factors. It is a broad diagnosis encompassing a wide variety of phenotypes and severities from simple ID to complex dysmorphia, epilepsia, autism spectrum disorder (ASD). 15% to 40% of ID is due to genetic factors [2]. Chromosomal copy number variations (CNVs) are known to be an important component of genetic variants and play an important role in the etiology of ID [3]
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