PDF(Pubmed)
Abstract：
Mutations in the KLHL40 gene are a common cause of severe or even lethal nemaline myopathy. Some cases with mild forms have been described, although the cases are still anecdotal. The aim of this paper was to systematically review the cases described in the literature and to describe a 12-year clinical and imaging follow-up in an Italian patient with KLHL40- related myopathy in order to suggest possible follow-up measurements.
Having searched through three electronic databases (PubMed, Scopus, and EBSCO), 18 articles describing 65 patients with homozygous or compound heterozygous KLHL40 mutations were selected. A patient with a KLHL40 homozygous mutation (c.1582G>A/p.E528K) was added and clinical and genetic data were collected.
The most common mutation identified in our systematic review was the (c.1516A>C) followed by the (c.1582G>A). In our review, 60% percent of the patients died within the first 4 years of life. Clinical features were similar across the sample. Unfortunately, however, there is no record of the natural history data in the surviving patients. The 12-year follow-up of our patient revealed a slow improvement in her clinical course, identifying muscle MRI as the only possible marker of disease progression.
Due to its clinical and genotype homogeneity, KLHL40-related myopathy may be a condition that would greatly benefit from the development of new gene therapies; muscle MRI could be a good biomarker to monitor disease progression.
Having searched through three electronic databases (PubMed, Scopus, and EBSCO), 18 articles describing 65 patients with homozygous or compound heterozygous KLHL40 mutations were selected. A patient with a KLHL40 homozygous mutation (c.1582G>A/p.E528K) was added and clinical and genetic data were collected.
The most common mutation identified in our systematic review was the (c.1516A>C) followed by the (c.1582G>A). In our review, 60% percent of the patients died within the first 4 years of life. Clinical features were similar across the sample. Unfortunately, however, there is no record of the natural history data in the surviving patients. The 12-year follow-up of our patient revealed a slow improvement in her clinical course, identifying muscle MRI as the only possible marker of disease progression.
Due to its clinical and genotype homogeneity, KLHL40-related myopathy may be a condition that would greatly benefit from the development of new gene therapies; muscle MRI could be a good biomarker to monitor disease progression.
摘要：
背景：KLHL40基因突变是严重甚至致死性线虫肌病的常见原因。已经描述了一些轻度形式的病例，尽管这些病例仍然是轶事。本文的目的是系统地回顾文献中描述的病例，并描述一名意大利KLHL40相关肌病患者的12年临床和影像学随访，以建议可能的随访措施。
方法：搜索了三个电子数据库（PubMed，Scopus,和EBSCO)，选择了18篇文章，描述了65例具有纯合或复合杂合子KLHL40突变的患者。具有KLHL40纯合突变的患者（c.1582G>A/p。添加E528K），并收集临床和遗传数据。
结果：在我们的系统评价中确定的最常见的突变是（c.1516A>C），其次是（c.1582G>A）。在我们的审查中,60%的患者在生命的前4年内死亡。整个样品的临床特征相似。不幸的是,然而,没有存活患者的自然史数据记录.对我们的患者进行了12年的随访，发现她的临床过程缓慢改善，确定肌肉MRI是疾病进展的唯一可能标志。
结论：由于其临床和基因型同质性，KLHL40相关肌病可能是一种将极大受益于新基因疗法开发的疾病；肌肉MRI可能是监测疾病进展的良好生物标志物。
方法：搜索了三个电子数据库（PubMed，Scopus,和EBSCO)，选择了18篇文章，描述了65例具有纯合或复合杂合子KLHL40突变的患者。具有KLHL40纯合突变的患者（c.1582G>A/p。添加E528K），并收集临床和遗传数据。
结果：在我们的系统评价中确定的最常见的突变是（c.1516A>C），其次是（c.1582G>A）。在我们的审查中,60%的患者在生命的前4年内死亡。整个样品的临床特征相似。不幸的是,然而,没有存活患者的自然史数据记录.对我们的患者进行了12年的随访，发现她的临床过程缓慢改善，确定肌肉MRI是疾病进展的唯一可能标志。
结论：由于其临床和基因型同质性，KLHL40相关肌病可能是一种将极大受益于新基因疗法开发的疾病；肌肉MRI可能是监测疾病进展的良好生物标志物。
