＜シンポジウム（2）―10―3＞ここまで分かった筋疾患
顔面肩甲上腕型筋ジストロフィー
林 由起子1）2）, 後藤 加奈子1）2）, 西野 一三1）2）
1）国立精神・神経医療研究センター神経研究所疾病研究第一部〔〒187―8502 東京都小平市小川東町4―1―1〕
2）同トランスレーショナルメディカルセンター臨床開発部
Facioscapulohumeral muscular dystrophy (FSHD) is a common autosomal dominant muscular dystrophy caused by truncation of D4Z4 repeat array on chromosome 4q35. Facial and shoulder-girdle muscles are preferentially affected but clinical symptoms are quite variable even within the same family. Asymmetrical muscle involvement is also characteristic in this disease. There are no disease specific changes on muscle pathology, and genetic diagnosis is performed by the southern blotting analysis. Recent advances provide us several ideas on possible pathomechanisms of this complicated disease. There are several genes on chromosome 4q35 region including DUX4 within D4Z4 repeats. Transcription of these genes is usually repressed by epigenetic modifications of this chromosomal region and also accumulation of transcriptional repressors to the repeat array. Shortening of the D4Z4 repeats observed in FSHD can cause structural changes of this chromosomal region, reduced recruitment of repressors, and expression of noncoding RNA which can enhance transcription of the genes on chromosome 4q35 region. Actually, increased mRNA expression levels of 4q35 genes was reported in FSHD cells, together with their undesirable roles on muscles by overexpression models. Further analysis is required to elucidate the precise pathomechanisms of FSHD.
Full Text of this Article in Japanese PDF (304K)
(臨床神経, 52：1154−1157, 2012)
key words：テロメア，D4Z4リピート，エピジェネティクス，サザンブロット，遺伝子発現
（受付日：2012年5月24日）
