Primary collagen VI deficiency is the second most common congenital muscular dystrophy in Japan
Primary collagen VI deficiency is the second most common congenital muscular dystrophy in Japan
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DOI：
10.1212/01.wnl.0000271387.10404.4e
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发表时间：
2007-09-04
期刊：
影响因子：
9.9
通讯作者：
Nishino, I.
中科院分区：
文献类型：
--
作者：
Okada, M.;Kawahara, G.;Nishino, I.
目的：确定日本先天性肌营养不良症（CMD）中原发性VI型胶原缺乏症的频率，并建立基因型-表型相关性。研究方法：我们进行了免疫组化VI胶原蛋白的肌肉从362例日本CMD患者，并直接测序的三个VI胶原蛋白基因，COL 6A 1，COL 6A 2，和COL 6A 3，在患者中发现有VI胶原蛋白deficiency.Results：在日本，原发性VI胶原蛋白缺乏症占7.2%的先天性肌肉缺乏症。在这些患者中，5例完全缺乏（CD），29例肌膜特异性VI型胶原缺乏症（SSCD）。我们在所有5名CD患者中发现了COL 6A 2和COL 6A 3的两个纯合突变和三个复合杂合突变，并在21名SSCD患者中鉴定了COL 6A 1、COL 6A 2和COL 6A 3的三螺旋结构域（THD）中的杂合错义突变或框内小缺失。所有SSCD突变均为散发性显性突变。结论：原发性VI型胶原缺乏症是日本仅次于福山型CMD的第二常见CMD。位于COL 6A 1、COL 6A 2和COL 6A 3的THD中的半胱氨酸残基的N-末端侧的显性突变与SSCD密切相关。
Objectives: To determine the frequency of primary collagen VI deficiency in congenital muscular dystrophy ( CMD) in Japan and to establish the genotype-phenotype correlation. Methods: We performed immunohistochemistry for collagen VI in muscles from 362 Japanese patients with CMD, and directly sequenced the three collagen VI genes, COL6A1, COL6A2, and COL6A3, in patients found to have collagen VI deficiency.Results: In Japan, primary collagen VI deficiency accounts for 7.2% of congenital muscular deficiency. Among these patients, five had complete deficiency ( CD) and 29 had sarcolemma-specific collagen VI deficiency ( SSCD). We found two homozygous and three compound heterozygous mutations in COL6A2 and COL6A3 in all five patients with CD, and identified heterozygous missense mutations or in-frame small deletions in 21 patients with SSCD in the triple helical domain ( THD) of COL6A1, COL6A2, and COL6A3. All mutations in SSCD were sporadic dominant. No genotype-phenotype correlation was seen.Conclusion: Primary collagen VI deficiency is the second most common CMD after Fukuyama type CMD in Japan. Dominant mutations located in the N-terminal side from the cysteine residue in the THD of COL6A1, COL6A2, and COL6A3 are closely associated with SSCD.