A novel autosomal recessive myopathy with external ophthalmoplegia linked to chromosome 17p13.1-p12
A novel autosomal recessive myopathy with external ophthalmoplegia linked to chromosome 17p13.1-p12
复制标题
DOI：
10.1093/brain/awh338
复制
发表时间：
2005-01-01
期刊：
影响因子：
14.5
通讯作者：
Argov, Z
中科院分区：
文献类型：
--
作者：
Lossos, A;Baala, L;Argov, Z
我们描述了一种新的常染色体隐性肌病，其发病早、进展非常缓慢，其特征是来自一个大型且高度近亲繁殖的阿拉伯社区的 8 个家庭的 16 名受试者的明显的外部眼肌麻痹。典型的临床特征包括轻度面部和骨骼肌无力以及上肢近端萎缩更为明显、与共轭相关的面部畸形和脊柱侧弯、向上凝视时最严重的非限制性眼球运动障碍，并且没有上睑下垂或眼球运动异常。患者的眼眶 MRI 显示眼旋转肌因脂肪替代而萎缩。骨骼肌活检的主要病理改变是明显的 1 型纤维优势，并具有核心状结构。对来自两个信息丰富的家族的受影响成员的纯合性区域进行全基因组搜索，确定了与染色体 17p13.1-p12 标记的连锁。在位点 D17S1803 和 AFMA070WD1 处获得了优势分数的最大两点对数（Zmax = 3.74，theta = 0）。 D17S1812 和 D17S947 处的两次独立重组事件进一步定义了 12 cM 的关键区域。几个基因映射到这个区间，包括一组肌节肌球蛋白重链基因。其中一个基因 MYH2 与 3 号包涵体肌病有关，但直接测序未发现外显子突变。这种新肌病的分子基础仍有待确定。
We describe a new autosomal recessive myopathy of early onset and very slow progression distinguished by the prominent external ophthalmoplegia in 16 subjects of eight families from a large and highly inbred Arab community. Characteristic clinical features include mild facial and skeletal muscle weakness and atrophy more pronounced proximally in the upper limbs, facial dysmorphism and scoliosis associated with conjugate, non-restrictive ocular motility impairment greatest in the upgaze and without ptosis or aberrant eye movements. Orbital MRI in the patients demonstrated atrophy with fatty replacement of the oculorotatory muscles. The major pathological alteration on skeletal muscle biopsy was a marked type 1 fibre predominance with core-like formations. A genome wide search for regions of homozygosity in the affected members from two informative families identified linkage with chromosome 17p13.1-p12 markers. Maximum two-point logarithm of odds scores were obtained at loci D17S1803 and AFMA070WD1 (Zmax = 3.74 at theta = 0). Two independent recombination events at D17S1812 and D17S947 further defined a critical region of 12 cM. Several genes map to this interval, including a cluster of sarcomeric myosin heavy chain genes. One of these genes, MYH2, is involved in inclusion body myopathy 3, but no exonic mutations were found by direct sequencing. The molecular basis for this new myopathy remains to be identified.