全外显子组测序和甲基化分析在解开复杂的面肩胛骨-肱骨肌营养不良病例中的作用。

IF 2.3 3区 医学 Q2 GENETICS & HEREDITY
Francesca Torri, Claudia Strafella, Liliana Vercelli, Giulio Gadaleta, Barbara Risi, Domenica Megalizzi, Luca Colantoni, Beatrice Ciurli, Mariaconcetta Rende, Massimiliano Filosto, Tiziana Mongini, Gabriele Siciliano, Emiliano Giardina, Giulia Ricci
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引用次数: 0

摘要

尽管观察到广泛的临床表现,但面肩肱肌营养不良症具有独特的表型特征,可能反映了不同的疾病进展速度或复杂的遗传机制。迄今为止,FSHD的诊断标准依赖于确定疾病的遗传特征(减少D4Z4等位基因,允许4q等位基因,低甲基化,以及在某些情况下修饰基因的变异)。然而,解释遗传数据需要与表型密切相关,特别是在非典型病例中。该研究纳入了42例D4Z4收缩或属于DRAs分离谱系的患者,但根据综合临床评估表(CCEF),由于表现出非典型临床特征或意外疾病严重程度而被选中。42人进行了4q亚型分析、DNA甲基化评估、全外显子组测序(WES)和分离分析。在24例病例中,WES发现了与不同神经肌肉疾病相关的基因中可能的致病性或致病性变异,在某些情况下可能与观察到的表型相容。甲基化分析证明有助于区分无症状和非典型病例,提示鉴别诊断。我们的研究结果强调了对疑似FSHD患者进行详细表型表征的重要性,并且在非典型表型的情况下,将D4Z4分级与其他程序(如WES)相结合。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Role of Whole-Exome Sequencing and Methylation Analysis in Untangling Complex Facioscapulo-Humeral Muscular Dystrophy Cases.

Facioscapulo-humeral muscular dystrophy is characterized by a distinctive phenotype, although a wide range of clinical expressions is observed, possibly reflecting different disease progression rates or complex genetic mechanisms. To date, the diagnostic criteria for FSHD rely on identifying the genetic signature of the disease (reduced D4Z4 allele, permissive 4q allele, hypomethylation, and in some cases variants in modifier genes). However, interpreting genetic data requires careful correlation with the phenotype, especially in atypical cases. The study included a cohort of 42 patients with a D4Z4 contraction or belonging to a pedigree in which DRAs segregated but who were selected due to presenting atypical clinical features or an unexpected disease severity according to the Comprehensive Clinical Evaluation Form (CCEF). The 42 underwent 4q subtype analysis, DNA methylation assessment, whole-exome sequencing (WES) and segregation analysis. In 24 cases, WES identified likely pathogenic or pathogenic variants in genes associated with different neuromuscular disorders, in some cases possibly compatible with the observed phenotype. Methylation analysis proved useful in distinguishing asymptomatic and atypical cases, prompting differential diagnosis. Our results emphasize the importance of a detailed phenotypic characterization of patients with a suspicion of FSHD and, in the case of atypical phenotypes, the combination of D4Z4 sizing with other procedures such as WES.

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来源期刊
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
期刊介绍: Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
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