贝思伦肌病基因座异质性及与2q37连锁的证据。

Evidence for locus heterogeneity in the Bethlem myopathy and linkage to 2q37.

作者信息

Speer M C, Tandan R, Rao P N, Fries T, Stajich J M, Bolhuis P A, Jöbsis G J, Vance J M, Viles K D, Sheffield K, James C, Kahler S G, Pettenati M, Gilbert J R, Denton P H, Yamaoka L H, Pericak-Vance M A

机构信息

Division of Neurology, Duke University Medical Center, Durham, NC 27710, USA.

出版信息

Hum Mol Genet. 1996 Jul;5(7):1043-6. doi: 10.1093/hmg/5.7.1043.

DOI:10.1093/hmg/5.7.1043

PMID:8817344

Abstract

The Bethlem myopathy, a childhood onset autosomal dominant myopathy with joint contractures, has recently been localized to 21q in a series of Dutch families and the alpha 1 and alpha 2 subunits of type VI collagen (COL6A1 and COL6A2) have been postulated as candidate genes. We investigate a large family of French Canadian descent (family 1489) in which the Bethlem myopathy is segregating. Family 1489 is unlinked to the region of interest on 21q, thus demonstrating locus heterogeneity within the Bethlem myopathy classification. In view of the localization of the genes coding the alpha 1 and alpha 2 subunits of type VI collagen on chromosome 21q, we carried out linkage analysis on chromosome 2q where the alpha 3 subunit of type VI collagen has been localized. We demonstrate linkage to markers in this region, define the region of disease gene localization, and confirm by FISH analysis that COL6A3 is located within the interval of interest making COL6A3 a feasible candidate gene for the Bethlem myopathy.

摘要

贝斯勒姆肌病是一种伴有关节挛缩的儿童期起病的常染色体显性肌病，最近在一系列荷兰家族中被定位到21号染色体长臂，VI型胶原的α1和α2亚基（COL6A1和COL6A2）被推测为候选基因。我们研究了一个法裔加拿大家族（1489家族），其中贝斯勒姆肌病呈分离状态。1489家族与21号染色体长臂上的相关区域不连锁，从而证明了贝斯勒姆肌病分类中的基因座异质性。鉴于编码VI型胶原α1和α2亚基的基因定位于21号染色体长臂，我们对2号染色体进行了连锁分析，VI型胶原的α3亚基已定位在此染色体上。我们证明了与该区域标记的连锁关系，确定了疾病基因定位区域，并通过荧光原位杂交分析证实COL6A3位于相关区间内，使COL6A3成为贝斯勒姆肌病的一个可行候选基因。