Bakker E, Wijmenga C, Vossen R H, Padberg G W, Hewitt J, van der Wielen M, Rasmussen K, Frants R R
Clinical Genetics Center, Leiden University, The Netherlands.
Muscle Nerve Suppl. 1995;2:S39-44.
Facioscapulohumeral muscular dystrophy (FSHD) has recently been shown to be associated with deletions that are detectable using probe p13E-11 (D4F104S1). Although these deletions reside within large, highly polymorphic restriction fragments (20-300 kb), the "mutant" fragment is usually shorter than 28 kb and can routinely be detected using conventional agarose gel electrophoresis. Yet, the complete visualization of the alleles requires pulsed-field gel electrophoresis (PFGE). Family studies showed that p13E-11 detects two nonallelic loci in this size range, only one of which originates from chromosome 4q35. We have assigned the other p13E-11 locus to chromosome 10qter by linkage analysis in CEPH pedigrees. Knowing the location of both loci improves the diagnostic reliability, as the exact origin of "small" EcoRI fragments can be determined by haplotyping. Since FSHD shows genetic heterogeneity, this 10qter locus became an interesting candidate to be the second FSHD locus. However, analysis of a large chromosome 4-unlinked FSHD family did not provide evidence for linkage on chromosome 10qter.
面肩肱型肌营养不良症（FSHD）最近被证明与使用探针p13E - 11（D4F104S1）可检测到的缺失相关。尽管这些缺失存在于大的、高度多态性的限制性片段（20 - 300 kb）内，但“突变”片段通常短于28 kb，并且可以使用常规琼脂糖凝胶电泳常规检测到。然而，等位基因的完整可视化需要脉冲场凝胶电泳（PFGE）。家系研究表明，p13E - 11在这个大小范围内检测到两个非等位基因座，其中只有一个起源于染色体4q35。我们通过对CEPH家系的连锁分析将另一个p13E - 11基因座定位到染色体10qter。了解这两个基因座的位置可提高诊断可靠性，因为“小”EcoRI片段的确切起源可以通过单倍型分析来确定。由于FSHD表现出遗传异质性，这个10qter基因座成为第二个FSHD基因座的一个有趣候选者。然而，对一个大的与染色体4无连锁关系的FSHD家系的分析并未提供染色体10qter上连锁的证据。
