Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy.
Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy.
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常染色体隐性遗传福山先天性肌营养不良症杂合性对 X 染色体连锁肌营养不良蛋白异常表达的可能影响。
DOI：
10.1073/pnas.89.2.623
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发表时间：
1992
影响因子：
11.1
通讯作者：
Kunkel,LM
中科院分区：
文献类型：
--
作者：
Beggs,AH;Neumann,PE;Arahata,K;Arikawa,E;Nonaka,I;Anderson,MS;Kunkel,LM
肌营养不良蛋白（一种肌肉和神经的细胞骨架蛋白）的异常通常被认为是杜兴肌营养不良症和贝克肌营养不良症的特有症状。然而，最近发现几名患者患有肌营养不良蛋白缺乏症，在进行肌营养不良蛋白检测之前，根据临床发现，他们被认为患有福山先天性肌营养不良症（FCMD）。流行病学数据表明，只有 1/3500 患有常染色体隐性遗传 FCMD 的男性应该有异常肌营养不良蛋白。为了解释对 3/23 具有异常肌营养不良蛋白的 FCMD 男性的观察结果，我们提出肌营养不良蛋白和 FCMD 基因产物相互作用，并且这些患者表型（相对于杜氏肌营养不良症）的较早发病和更严重的原因是他们除了杜氏肌营养不良症是半合子外，还因为他们是 FCMD 突变杂合子，杜氏肌营养不良症是一种预计发生在1/175,000 日本男性。该模型可能有助于解释 FCMD 患者中一些临床和病理变异的遗传基础，并且对于理解其他常染色体隐性遗传疾病的遗传具有潜在的意义。例如，由与 X 染色体连锁基因产物相互作用的蛋白质突变引起的罕见常染色体隐性遗传疾病的性别比例可能会出现可预测的 1:1 偏差。
Abnormalities of dystrophin, a cytoskeletal protein of muscle and nerve, are generally considered specific for Duchenne and Becker muscular dystrophy. However, several patients have recently been identified with dystrophin deficiency who, before dystrophin testing, were considered to have Fukuyama congenital muscular dystrophy (FCMD) on the basis of clinical findings. Epidemiologic data suggest that only 1/3500 males with autosomal recessive FCMD should have abnormal dystrophin. To explain the observation of 3/23 FCMD males with abnormal dystrophin, we propose that dystrophin and the FCMD gene product interact and that the earlier onset and greater severity of these patients' phenotype (relative to Duchenne muscular dystrophy) are due to their being heterozygous for the FCMD mutation in addition to being hemizygous for Duchenne muscular dystrophy, a genotype that is predicted to occur in 1/175,000 Japanese males. This model may help explain the genetic basis for some of the clinical and pathological variability seen among patients with FCMD, and it has potential implications for understanding the inheritance of other autosomal recessive disorders in general. For example, sex ratios for rare autosomal recessive disorders caused by mutations in proteins that interact with X chromosome-linked gene products may display predictable deviation from 1:1.