The usefulness of array comparative genomic hybridization in clinical diagnostics of intellectual disability in children

Dev Period Med. 2014 Jul-Sep;18(3):307-17.

Abstract

Introduction: Intellectual disability (ID)/Developmental delay (DD), which occurs in 1-3% of the population, accounts for a large number of cases regularly seen in genetics clinics. Currently, Array Comparative Genomic Hybridization (array CGH) is recommended by the International Standards for Cytogenomic Arrays (ISCA) Consortium as a first line test in the diagnostics of ID/DD, replacing G-banded chromosome analysis.

The aim: Application of array CGH in clinical diagnostics of developmental delay/ intellectual disability in children.

Material and methods: We present the results of 8x60K oligonucleotide array application that was successfully implemented in a cohort of 112 patients with the clinical diagnosis of intellectual disability and accompanying dysmorphic features and/or congenital malformations.

Results: We have identified 37 copy number variants (CNVs) with the size ranging from 40 kb to numerical chromosomal aberrations, including unbalanced translocations and chromosome Y disomy, receiving an overall diagnostic yield of 33%. Known pathogenic changes were identified in 21.4% of the cases. Among patients with pathogenic CNVs identified by array CGH, 41.7% had a previously normal karyotype analysis.

Conclusions: Our studies provide more insights into the benefits derived by using chromosomal microarray analysis and demonstrate the usefulness of array CGH as a first-tier clinical setting test in patients with intellectual disability.

Publication types

  • Evaluation Study

MeSH terms

  • Abnormalities, Multiple / diagnosis*
  • Abnormalities, Multiple / genetics*
  • Adolescent
  • Adult
  • Body Dysmorphic Disorders / diagnosis
  • Body Dysmorphic Disorders / genetics
  • Child
  • Child, Preschool
  • Chromosome Aberrations
  • Comparative Genomic Hybridization / methods*
  • DNA Copy Number Variations
  • Developmental Disabilities / diagnosis*
  • Developmental Disabilities / genetics*
  • Diagnosis, Differential
  • Female
  • Humans
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / genetics*
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Young Adult