title: Clinical application of array-based comparative genomic hybridization by two-stage screening for 536 patients with mental retardation and multiple congenital anomalies.
abstract: Recent advances in the analysis of patients with congenital abnormalities using array-based comparative genome hybridization (aCGH) have uncovered two types of genomic copy-number variants (CNVs); pathogenic CNVs (pCNVs) relevant to congenital disorders and benign CNVs observed also in healthy populations, complicating the screening of disease-associated alterations by aCGH. To apply the aCGH technique to the diagnosis as well as investigation of multiple congenital anomalies and mental retardation (MCA/MR), we constructed a consortium with 23 medical institutes and hospitals in Japan, and recruited 536 patients with clinically uncharacterized MCA/MR, whose karyotypes were normal according to conventional cytogenetics, for two-stage screening using two types of bacterial artificial chromosome-based microarray. The first screening using a targeted array detected pCNV in 54 of 536 cases (10.1%), whereas the second screening of the 349 cases negative in the first screening using a genome-wide high-density array at intervals of approximately 0.7 Mb detected pCNVs in 48 cases (13.8%), including pCNVs relevant to recently established microdeletion or microduplication syndromes, CNVs containing pathogenic genes and recurrent CNVs containing the same region among different patients. The results show the efficient application of aCGH in the clinical setting.
authors.affiliation: Department of Molecular Cytogenetics, School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Hayashi
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Aizu
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Mizuno
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurosawa
authors.forename: Nana
authors.initials: N
authors.lastname: Okamoto
authors.forename: Shozo
authors.initials: S
authors.lastname: Honda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Araki
authors.forename: Shuki
authors.initials: S
authors.lastname: Mizutani
authors.forename: Hironao
authors.initials: H
authors.lastname: Numabe
authors.forename: Shinji
authors.initials: S
authors.lastname: Saitoh
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kosho
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Fukushima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitsubuchi
authors.forename: Fumio
authors.initials: F
authors.lastname: Endo
authors.forename: Yasutsugu
authors.initials: Y
authors.lastname: Chinen
authors.forename: Rika
authors.initials: R
authors.lastname: Kosaki
authors.forename: Torayuki
authors.initials: T
authors.lastname: Okuyama
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ohki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshihashi
authors.forename: Masae
authors.initials: M
authors.lastname: Ono
authors.forename: Fumio
authors.initials: F
authors.lastname: Takada
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ono
authors.forename: Mariko
authors.initials: M
authors.lastname: Yagi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Makita
authors.forename: Akira
authors.initials: A
authors.lastname: Hata
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D022202:Chromosomes, Artificial, Bacterial; D055028:Comparative Genomic Hybridization / Q000379:methods*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D007564:Japan; D007621:Karyotyping; D013577:Syndrome