title: Clinical implementation of chromosomal microarray analysis: summary of 2513 postnatal cases.
abstract: BACKGROUND
  Array Comparative Genomic Hybridization (a-CGH) is a powerful molecular cytogenetic tool to detect genomic imbalances and study disease mechanism and pathogenesis. We report our experience with the clinical implementation of this high resolution human genome analysis, referred to as Chromosomal Microarray Analysis (CMA).
  
  
  RESULTS
  CMA was performed clinically on 2513 postnatal samples from patients referred with a variety of clinical phenotypes. The initial 775 samples were studied using CMA array version 4 and the remaining 1738 samples were analyzed with CMA version 5 containing expanded genomic coverage. Overall, CMA identified clinically relevant genomic imbalances in 8.5% of patients: 7.6% using V4 and 8.9% using V5. Among 117 cases referred for additional investigation of a known cytogenetically detectable rearrangement, CMA identified the majority (92.5%) of the genomic imbalances. Importantly, abnormal CMA findings were observed in 5.2% of patients (98/1872) with normal karyotypes/FISH results, and V5, with expanded genomic coverage, enabled a higher detection rate in this category than V4. For cases without cytogenetic results available, 8.0% (42/524) abnormal CMA results were detected; again, V5 demonstrated an increased ability to detect abnormality. Improved diagnostic potential of CMA is illustrated by 90 cases identified with 51 cryptic microdeletions and 39 predicted apparent reciprocal microduplications in 13 specific chromosomal regions associated with 11 known genomic disorders. In addition, CMA identified copy number variations (CNVs) of uncertain significance in 262 probands; however, parental studies usually facilitated clinical interpretation. Of these, 217 were interpreted as familial variants and 11 were determined to be de novo; the remaining 34 await parental studies to resolve the clinical significance.
  
  
  CONCLUSIONS
  This large set of clinical results demonstrates the significantly improved sensitivity of CMA for the detection of clinically relevant genomic imbalances and highlights the need for comprehensive genetic counseling to facilitate accurate clinical correlation and interpretation.
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors: Xinyan
authors: X
authors: Lu
authors: Chad A
authors: CA
authors: Shaw
authors: Ankita
authors: A
authors: Patel
authors: Jiangzhen
authors: J
authors: Li
authors: M Lance
authors: ML
authors: Cooper
authors: William R
authors: WR
authors: Wells
authors: Cathy M
authors: CM
authors: Sullivan
authors: Trilochan
authors: T
authors: Sahoo
authors: Svetlana A
authors: SA
authors: Yatsenko
authors: Carlos A
authors: CA
authors: Bacino
authors: Pawel
authors: P
authors: Stankiewicz
authors: Zhishu
authors: Z
authors: Ou
authors: A Craig
authors: AC
authors: Chinault
authors: Arthur L
authors: AL
authors: Beaudet
authors: James R
authors: JR
authors: Lupski
authors: Sau W
authors: SW
authors: Cheung
authors: Patricia A
authors: PA
authors: Ward
mesh_terms: D022981:Allelic Imbalance / Q000235:genetics; D002877:Chromosomes, Human / Q000235:genetics*; D055028:Comparative Genomic Hybridization / Q000379:methods*; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D007231:Infant, Newborn; D007621:Karyotyping; D046228:Microarray Analysis / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010641:Phenotype; D012016:Reference Values