@article{8dc07eed8e6c472e8426907de1222ec0,
title = "Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies",
abstract = "Chromosomal microarray (CMA) is increasingly utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). Performing CMA and G-banded karyotyping on every patient substantially increases the total cost of genetic testing. The International Standard Cytogenomic Array (ISCA) Consortium held two international workshops and conducted a literature review of 33 studies, including 21,698 patients tested by CMA. We provide an evidence-based summary of clinical cytogenetic testing comparing CMA to G-banded karyotyping with respect to technical advantages and limitations, diagnostic yield for various types of chromosomal aberrations, and issues that affect test interpretation. CMA offers a much higher diagnostic yield (15%-20%) for genetic testing of individuals with unexplained DD/ID, ASD, or MCA than a G-banded karyotype (∼3%, excluding Down syndrome and other recognizable chromosomal syndromes), primarily because of its higher sensitivity for submicroscopic deletions and duplications. Truly balanced rearrangements and low-level mosaicism are generally not detectable by arrays, but these are relatively infrequent causes of abnormal phenotypes in this population (<1%). Available evidence strongly supports the use of CMA in place of G-banded karyotyping as the first-tier cytogenetic diagnostic test for patients with DD/ID, ASD, or MCA. G-banded karyotype analysis should be reserved for patients with obvious chromosomal syndromes (e.g., Down syndrome), a family history of chromosomal rearrangement, or a history of multiple miscarriages.",
author = "Miller, {David T.} and Adam, {Margaret P.} and Swaroop Aradhya and Biesecker, {Leslie G.} and Brothman, {Arthur R.} and Carter, {Nigel P.} and Church, {Deanna M.} and Crolla, {John A.} and Eichler, {Evan E.} and Epstein, {Charles J.} and Faucett, {W. Andrew} and Lars Feuk and Friedman, {Jan M.} and Ada Hamosh and Laird Jackson and Kaminsky, {Erin B.} and Klaas Kok and Krantz, {Ian D.} and Kuhn, {Robert M.} and Charles Lee and Ostell, {James M.} and Carla Rosenberg and Scherer, {Stephen W.} and Spinner, {Nancy B.} and Stavropoulos, {Dimitri J.} and Tepperberg, {James H.} and Thorland, {Erik C.} and Vermeesch, {Joris R.} and Waggoner, {Darrel J.} and Watson, {Michael S.} and Martin, {Christa Lese} and Ledbetter, {David H.}",
note = "Funding Information: Workshops and conference calls related to the ISCA Consortium were funded through a grant from the ACMG Foundation and Luminex to D.H.L. and C.L.M., and ongoing standards and database development are funded in part by grants from the National Institutes of Health (RC2HD064525 and MH074090 to D.H.L. and C.L.M.). This work was also supported by Simons Foundation grant 137578 (to E.E.E.). E.E.E. is an investigator of the Howard Hughes Medical Institute. The opinions expressed here are those of the authors and the ISCA Consortium and do not necessarily reflect the views of the institutions to which the authors are affiliated, the ACMG, or the American Society of Human Genetics (ASHG). The authors would like to thank Dr. Omer Gokcumen for his assistance with summary of population CNV data. Regarding conflict of interest, the majority of authors are involved in CMA testing and/or cytogenetic testing, either as clinicians who order the testing, laboratory professionals who perform the testing, or researchers in the genomics field. S.A. is a director of clinical cytogenetics at GeneDx, a subsidiary of BioReference Laboratories; A.R.B. is a director of clinical cytogenetics and molecular cytogenetics at ARUP Laboratories; E.E.E. is a member of the Pacific Biosciences Scientific Advisory Board. S.W.S. is on the Scientific Advisory Board of Combimatrix Diagnostics and the Scientific Advisory Committee of Autism Speaks. J.T. is a director of clinical cytogenetics at Laboratory Corporation of America. J.V. is on the board of directors of Cartagenia. M.W. raises funds from industry to support the educational activities of the ACMG Foundation. ",
year = "2010",
month = may,
day = "14",
doi = "10.1016/j.ajhg.2010.04.006",
language = "English (US)",
volume = "86",
pages = "749--764",
journal = "American journal of human genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "5",
}