title: Clinical utility of the X-chromosome array.
abstract: Previous studies have limited the use of specific X-chromosome array designed platforms to the evaluation of patients with intellectual disability. In this retrospective analysis, we reviewed the clinical utility of an X-chromosome array in a variety of scenarios. We divided patients according to the indication for the test into four defined categories: (1) autism spectrum disorders and/or developmental delay and/or intellectual disability (ASDs/DD/ID) with known family history of neurocognitive disorders; (2) ASDs/DD/ID without known family history of neurocognitive disorders; (3) breakpoint definition of an abnormality detected by a different cytogenetic test; and (4) evaluation of suspected or known X-linked conditions. A total of 59 studies were ordered with 27 copy number variants detected in 25 patients (25/59 = 42%). The findings were deemed pathogenic/likely pathogenic (16/59 = 27%), benign (4/59 = 7%) or uncertain (7/59 = 12%). We place particular emphasis on the utility of this test for the diagnostic evaluation of families affected with X-linked conditions and how it compares to whole genome arrays in this setting. In conclusion, the X-chromosome array frequently detects genomic alterations of the X chromosome and it has advantages when evaluating some specific X-linked conditions. However, careful interpretation and correlation with clinical findings is needed to determine the significance of such changes. When the X-chromosome array was used to confirm a suspected X-linked condition, it had a yield of 63% (12/19) and was useful in the evaluation and risk assessment of patients and families.
authors.affiliation: Greenwood Genetic Center, Greenwood, SC, USA. yzarate@ggc.org
authors.forename: Yuri A
authors.initials: YA
authors.lastname: Zarate
authors.forename: Alka
authors.initials: A
authors.lastname: Dwivedi
authors.forename: Frank O
authors.initials: FO
authors.lastname: Bartel
authors.forename: M Allison
authors.initials: MA
authors.lastname: Bellomo
authors.forename: Sara S
authors.initials: SS
authors.lastname: Cathey
authors.forename: Neena L
authors.initials: NL
authors.lastname: Champaigne
authors.forename: L Kate
authors.initials: LK
authors.lastname: Clarkson
authors.forename: Barbara R
authors.initials: BR
authors.lastname: Dupont
authors.forename: David B
authors.initials: DB
authors.lastname: Everman
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Geer
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Gordon
authors.forename: Angie W
authors.initials: AW
authors.lastname: Lichty
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lyons
authors.forename: R Curtis
authors.initials: RC
authors.lastname: Rogers
authors.forename: Robert A
authors.initials: RA
authors.lastname: Saul
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Schroer
authors.forename: Steven A
authors.initials: SA
authors.lastname: Skinner
authors.forename: Roger E
authors.initials: RE
authors.lastname: Stevenson
mesh_terms: D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics*; D056915:DNA Copy Number Variations; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D050172:Genes, X-Linked; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D055815:Young Adult