A family-based study into penetrance in facioscapulohumeral muscular dystrophy type 1

Objective: An observational cross-sectional study was conducted in a national facioscapulohumeral muscular dystrophy (FSHD) expertise center to estimate the penetrance of FSHD1 and to evaluate phenotype–genotype correlations.

Methods: Ten FSHD1 probands carrying 4–9 D4Z4 unit alleles and 140 relatives were examined. All 150 participants were genetically characterized, including D4Z4 methylation levels in the mutation carriers. Mutation carriers were classified as (1) symptomatic: with symptoms of muscle weakness on history and muscle FSHD signs on examination; (2) asymptomatic: without symptoms of muscle weakness but with muscle FSHD signs on examination; and (3) nonpenetrant: without symptoms of muscle weakness on history and without muscle FSHD signs on examination. We assessed the relationship between age-corrected clinical severity score and repeat size, sex, and D4Z4 methylation levels.

Results: The maximum likelihood estimates of symptomatic and those of symptomatic plus asy...

研究目的：本研究于国家级面肩肱型肌营养不良症（facioscapulohumeral muscular dystrophy, FSHD）专业诊疗中心开展一项观察性横断面研究，旨在评估FSHD1型的外显率，并探讨表型-基因型相关性。
研究方法：纳入10例携带4~9个D4Z4拷贝数等位基因的FSHD1先证者，以及140名家系亲属，总计150名受试者。对所有受试者进行基因分型检测，包括突变携带者的D4Z4甲基化水平检测。将突变携带者分为三类：(1) 有症状组：既往存在肌无力病史，且体格检查可见FSHD相关肌病体征；(2) 无症状组：无肌无力既往症状，但体格检查可见FSHD相关肌病体征；(3) 非外显组：既无肌无力既往病史，体格检查也未发现FSHD相关肌病体征。本研究还分析了年龄校正后的临床严重程度评分与重复序列拷贝数、性别及D4Z4甲基化水平之间的关联。
研究结果：有症状者及有症状合并无症状者的最大似然估计值……