title: Evaluating Japanese patients with the Marfan syndrome using high-throughput microarray-based mutational analysis of fibrillin-1 gene.
abstract: Marfan syndrome (MS) is an inherited connective tissue disorder, and detailed evaluations of multiple organ systems are required for its diagnosis. Genetic testing of the disease-causing fibrillin-1 gene (FBN1) is also important in this diagnostic scheme. The aim of this study was to define the clinical characteristics of Japanese patients with MS and enable the efficient and accurate diagnosis of MS with mutational analysis using a high-throughput microarray-based resequencing system. Fifty-three Japanese probands were recruited, and their clinical characteristics were evaluated using the Ghent criteria. For mutational analysis, an oligonucleotide microarray was designed to interrogate FBN1, and the entire exon and exon-intron boundaries of FBN1 were sequenced. Clinical evaluation revealed more pulmonary phenotypes and fewer skeletal phenotypes in Japanese patients with MS compared to Caucasians. The microarray-based resequencing system detected 35 kinds of mutations, including 23 new mutations. The mutation detection rate for patients who fulfilled the Ghent criteria reached 71%. Of note, splicing mutations accounted for 19% of all mutations, which is more than previously reported. In conclusion, this comprehensive approach successfully detected clinical phenotypes of Japanese patients with MS and demonstrated the usefulness and feasibility of this microarray-based high-throughput resequencing system for mutational analysis of MS.
authors: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Japan.
authors: Naomi
authors: N
authors: Ogawa
authors: Yasushi
authors: Y
authors: Imai
authors: Yuji
authors: Y
authors: Takahashi
authors: Kan
authors: K
authors: Nawata
authors: Kazuo
authors: K
authors: Hara
authors: Hiroshi
authors: H
authors: Nishimura
authors: Masayoshi
authors: M
authors: Kato
authors: Norifumi
authors: N
authors: Takeda
authors: Takahide
authors: T
authors: Kohro
authors: Hiroyuki
authors: H
authors: Morita
authors: Tsuyoshi
authors: T
authors: Taketani
authors: Tetsuro
authors: T
authors: Morota
authors: Tsutomu
authors: T
authors: Yamazaki
authors: Jun
authors: J
authors: Goto
authors: Shoji
authors: S
authors: Tsuji
authors: Shinichi
authors: S
authors: Takamoto
authors: Ryozo
authors: R
authors: Nagai
authors: Yasunobu
authors: Y
authors: Hirata
mesh_terms: D000328:Adult; D044466:Asian People; D005260:Female; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics*; D046228:Microarray Analysis