Clinical application of array-based comparative genomic hybridization by two-stage screening for 536 patients with mental retardation and multiple congenital anomalies.
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.
Hayashi
Shin
S
Department of Molecular Cytogenetics, School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan.
Imoto
Issei
I
Aizu
Yoshinori
Y
Okamoto
Nobuhiko
N
Mizuno
Seiji
S
Kurosawa
Kenji
K
Okamoto
Nana
N
Honda
Shozo
S
Araki
Satoshi
S
Mizutani
Shuki
S
Numabe
Hironao
H
Saitoh
Shinji
S
Kosho
Tomoki
T
Fukushima
Yoshimitsu
Y
Mitsubuchi
Hiroshi
H
Endo
Fumio
F
Chinen
Yasutsugu
Y
Kosaki
Rika
R
Okuyama
Torayuki
T
Ohki
Hirotaka
H
Yoshihashi
Hiroshi
H
Ono
Masae
M
Takada
Fumio
F
Ono
Hiroaki
H
Yagi
Mariko
M
Matsumoto
Hiroshi
H
Makita
Yoshio
Y
Hata
Akira
A
Inazawa
Johji
J
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