Cormand B, Avela K, Pihko H, Santavuori P, Talim B, Topaloglu H, de la Chapelle A, Lehesjoki A E
Department of Medical Genetics, University of Helsinki, Finland.
Am J Hum Genet. 1999 Jan;64(1):126-35. doi: 10.1086/302206.
Muscle-eye-brain disease (MEB) is an autosomal recessive disease of unknown etiology characterized by severe mental retardation, ocular abnormalities, congenital muscular dystrophy, and a polymicrogyria-pachygyria-type neuronal migration disorder of the brain. A similar combination of muscle and brain involvement is also seen in Walker-Warburg syndrome (WWS) and Fukuyama congenital muscular dystrophy (FCMD). Whereas the gene underlying FCMD has been mapped and cloned, the genetic location of the WWS gene is still unknown. Here we report the assignment of the MEB gene to chromosome 1p32-p34 by linkage analysis and homozygosity mapping in eight families with 12 affected individuals. After a genomewide search for linkage in four affected sib pairs had pinpointed the assignment to 1p, the MEB locus was more precisely assigned to a 9-cM interval flanked by markers D1S200 proximally and D1S211 distally. Multipoint linkage analysis gave a maximum LOD score of 6.17 at locus D1S2677. These findings provide a starting point for the positional cloning of the disease gene, which may play an important role in muscle function and brain development. It also provides an opportunity to test other congenital muscular dystrophy phenotypes, in particular WWS, for linkage to the same locus.
肌肉-眼-脑疾病（MEB）是一种病因不明的常染色体隐性疾病，其特征为严重智力发育迟缓、眼部异常、先天性肌营养不良以及大脑的多小脑回-巨脑回型神经元迁移障碍。在沃克-沃伯格综合征（WWS）和福山先天性肌营养不良（FCMD）中也可见到类似的肌肉和大脑受累情况。虽然FCMD的相关基因已被定位和克隆，但WWS基因的遗传定位仍然未知。在此，我们通过对8个家庭中12名患者进行连锁分析和纯合性定位，报告了MEB基因定位于染色体1p32 - p34。在对4对患病同胞进行全基因组连锁搜索将其定位于1p后，MEB基因座被更精确地定位于一个9厘摩的区间内，近端由标记D1S200侧翼，远端由标记D1S211侧翼。多点连锁分析在基因座D1S2677处给出了最大对数优势分数6.17。这些发现为疾病基因的定位克隆提供了一个起点，该基因可能在肌肉功能和大脑发育中起重要作用。它还提供了一个机会来测试其他先天性肌营养不良表型，特别是WWS，是否与同一基因座连锁。
