Aoki M, Liu J, Richard I, Bashir R, Britton S, Keers S M, Oeltjen J, Brown H E, Marchand S, Bourg N, Beley C, McKenna-Yasek D, Arahata K, Bohlega S, Cupler E, Illa I, Majneh I, Barohn R J, Urtizberea J A, Fardeau M, Amato A, Angelini C, Bushby K, Beckmann J S, Brown R H
Day Neuromuscular Research Laboratory, Massachusetts General Hospital East, Charlestown 02129, USA.
Neurology. 2001 Jul 24;57(2):271-8. doi: 10.1212/wnl.57.2.271.
Mutations in the skeletal muscle gene dysferlin cause two autosomal recessive forms of muscular dystrophy: Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B). The purpose of this study was to define the genomic organization of the dysferlin gene and conduct mutational screening and a survey of clinical features in 21 patients with defined molecular defects in the dysferlin gene.
Genomic organization of the gene was determined by comparing the dysferlin cDNA and genomic sequence in P1-derived artificial chromosomes (PACs) containing the gene. Mutational screening entailed conformational analysis and sequencing of genomic DNA and cDNA. Clinical records of patients with defined dysferlin gene defects were reviewed retrospectively.
The dysferlin gene encompasses 55 exons spanning over 150 kb of genomic DNA. Mutational screening revealed nine novel mutations associated with MM. The range of onset in this patient group was narrow with a mean of 19.0 +/- 3.9 years.
This study confirms that the dysferlin gene is mutated in MM and LGMD2B and extends understanding of the timing of onset of the disease. Knowledge of the genomic organization of the gene will facilitate mutation detection and investigations of the molecular biologic properties of the dysferlin gene.
骨骼肌基因dysferlin的突变会导致两种常染色体隐性遗传性肌营养不良症：宫下肌病（MM）和2B型肢带型肌营养不良症（LGMD2B）。本研究的目的是确定dysferlin基因的基因组结构，对21例dysferlin基因存在明确分子缺陷的患者进行突变筛查并调查其临床特征。
通过比较dysferlin cDNA与含有该基因的P1人工染色体（PAC）中的基因组序列来确定该基因的基因组结构。突变筛查包括基因组DNA和cDNA的构象分析及测序。对具有明确dysferlin基因缺陷的患者的临床记录进行回顾性分析。
dysferlin基因包含55个外显子，跨越超过150 kb的基因组DNA。突变筛查发现了9个与MM相关的新突变。该患者组的发病年龄范围较窄，平均为19.0 +/- 3.9岁。
本研究证实dysferlin基因在MM和LGMD2B中发生突变，并扩展了对该病发病时间的认识。该基因基因组结构的知识将有助于突变检测及对dysferlin基因分子生物学特性的研究。
