Heterogeneity in familial dominant Paget disease of bone and muscular dystrophy.
Heterogeneity in familial dominant Paget disease of bone and muscular dystrophy.
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骨和肌肉营养不良的家族性显性佩吉特病的异质性。
DOI：
10.1002/ajmg.10199
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Kimonis,VirginiaE
中科院分区：
文献类型：
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作者：
Waggoner,Brook;Kovach,MargaretJ;Winkelman,Marc;Cai,Dan;Khardori,Romesh;Gelber,David;Kimonis,VirginiaE
常染色体显性遗传的早发性佩吉特骨病（PDB）和肌营养不良症的结合是一种罕见的疾病。我们最近在伊利诺斯州中部的一个患有PDB和近端肢带型肌营养不良症（LGMD）的大家族中，以及另外3个患有遗传性包涵体肌病（HIBM）、骨佩吉特病和额颞叶痴呆症的家族中，将这种疾病定位到染色体9p21.1-q12上的一个独特位点。本研究描述了一个不相关的10人常染色体显性遗传PDB和肩胛腓骨型肌营养不良症家族。临床，生化和放射学评估进行了描述在这个家庭的临床特征。肌营养不良症的进展开始于腿部远端肌肉的无力，伴有足下垂。肌电图和肌肉活检与原发性营养不良相符。佩吉特病发病较早，平均年龄41岁，最初分布于长骨，最终浸润脊柱和骨盆。肌酸磷酸激酶（CPK）和碱性磷酸酶水平升高受影响的个人。分子分析排除了所有已知的佩吉特骨病、肩胛腓肌营养不良症（SPMD）、筋膜肩肱肌营养不良症（FSH）、肌萎缩侧索硬化症（ALS）、Bethlem肌病、两种常染色体显性肢带型肌营养不良症（LGMD）的基因座，以及染色体9p21.1-q12上LGMD或HIBM/PDB的关键区域，从而为肌营养不良症和佩吉特骨病的独特组合的家族间的遗传异质性提供了证据。© 2002 Wiley利斯公司
The combination of autosomal dominant, early onset Paget disease of bone (PDB) and muscular dystrophy is an unusual disorder. We recently mapped the disorder in a large family from central Illinois with PDB and proximal limb‐girdle type of muscular dystrophy (LGMD), and in 3 additional families with hereditary inclusion body myopathy (HIBM), Paget disease of bone and frontotemporal dementia, to a unique locus on chromosome 9p21.1‐q12. The present study describes an unrelated 10‐member family with autosomal dominant PDB and a scapuloperoneal type of muscular dystrophy. Clinical, biochemical, and radiological evaluations were performed to delineate clinical features in this family. Progression of the muscular dystrophy begins with weakness in the distal muscles of the legs accompanied by foot drop. EMG and muscle biopsy are compatible with a primary dystrophy. Onset of Paget disease is early, at a mean age of 41 years, with initial distribution in the long bones and eventual infiltration of the spine and pelvis. Creatine phosphokinase (CPK) and alkaline phosphatase levels are elevated in affected individuals. Molecular analyses excluded all known loci for Paget disease of bone, scapuloperoneal muscular dystrophy (SPMD), fascioscapulohumeral muscular dystrophy (FSH), amyotrophic lateral sclerosis (ALS), Bethlem myopathy, two forms of autosomal dominant limb‐girdle muscular dystrophy (LGMD), and the critical region for LGMD or HIBM/PDB on chromosome 9p21.1‐q12, thus providing evidence for genetic heterogeneity among families with the unique combination of muscular dystrophy and Paget disease of bone. © 2002 Wiley‐Liss, Inc.