Two-hit wonder: a novel genetic model to explain variable expressivity in severe pediatric phenotypes.

摘要

Genomic disorders involving microdeletions and microduplications have been reported in many individuals with neuropsychiatric disorders such as autism and mental retardation. The recurrent nature of these disorders is often explained by non-allelic homologous recombination (NAHR) mediated by large blocks of highly identical segmental duplications or low copy repeats (LCR). The rapidly growing list of genomic disorders is partly attributable to methodological advances in DNA microarray technologies that have enabled the identification of microscopic DNA losses and gains previously undetectable by standard cyto-genetic approaches. Knowledge of the prevalence and characteristics of recurrent microdeletions and microduplications is clinically invaluable; however, molecular diagnostics using copy number variant (CNV) data is frequently hampered by the phenomenon of 'variable expressivity' - when a phenotype is expressed to a different degree among individuals with the same genotype (or underlying mutation/CNV).