Abstract:

Females with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) mutations rarely exhibit clinical symptoms from childhood, although potential mechanisms for symptoms associated with DMD and BMD in females have been reported. We report the case of a female DMD patient with a clinical course indistinguishable from that of a male DMD patient, and who possessed compound heterozygous contiguous exon deletions in the dystrophin gene. She exhibited Gowers' sign, calf muscle hypertrophy, and a high serum creatine kinase level at 2 years. Her muscle pathology showed most of the fibers were negative for dystrophin immunohistochemical staining. She lost ambulation at 11 years. Multiplex ligation-dependent probe amplification analysis of this gene detected one copy of exons 48-53; she was found to be a BMD carrier with an in-frame deletion. Messenger RNA from her muscle demonstrated out-of-frame deletions of exons 48-50 and 51-53 occurring on separate alleles. Genomic DNA from her lymphocytes demonstrated the accurate deletion region on each allele. To our knowledge, this is the first report on a female patient possessing compound heterozygous contiguous exon deletions in the dystrophin gene, leading to DMD.

日本語要旨:

デュシェンヌ型筋ジストロフィー(DMD)とベッカー型筋ジストロフィー(BMD)はX連鎖劣性遺伝をとるため、原則として患者は男児に限られる。我々はDMD男児と同様の臨床経過を辿った女児を経験した。本症例は2歳でGowers徴候、腓腹筋肥大、CK高値を認め、11歳で歩行不能になった。筋肉組織ではジストロフィンが欠損していた。MLPA法でエクソン48-53の欠失(in-frame deletion)を認め、BMD症例と考えられたが、骨格筋mRNAとリンパ球由来ゲノムDNAのPCR解析ではエクソン48-50の欠失とエクソン51-53の欠失を各アレルに認めた(out-frame deletion)ことより、DMDと診断した。本症例は複合ヘテロ接合体変異によりDMDを呈した女児における初めての報告例である。