一种不寻常的兰尼碱受体 1（RYR1）表型：轻度以小腿为主的肌病。

An unusual ryanodine receptor 1 (RYR1) phenotype: Mild calf-predominant myopathy.

机构信息

From the Neuromuscular Research Center (M. Jokela, S.L., J.P., B.U.), Department of Neurology, University Hospital and University of Tampere; Division of Clinical Neurosciences (M. Jokela), Department of Neurology, Turku University Hospital and University of Turku; Kiinamyllynkatu 4-8 (M. Jokela), Turku, Finland; Unità Operativa Complessa di Neurologia (G.T.), Dipartimento di Scienze dell'Invecchiamento, Neurologiche, Ortopediche e della Testa-Collo, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Folkhälsan Institute of Genetics and Department of Medical Genetics (A.V., P.-H.J., S.V., M. Johari, M.S.), Haartman Institute, University of Helsinki, Finland; Institute of Pediatric Neurology (E.M., M.P.), Catholic University School of Medicine, Rome, Italy; Department of Pathology (S.H.), Fimlab Laboratories, Tampere University Hospital, Finland; Metabolic and Neuromuscular Unit (M.D.), Meyer Hospital, Florence, Italy; Department of Pediatric Neurology (P.I.), Children's Hospital, University of Helsinki and Helsinki University Hospital; Department of Neurology (P.H.), Kuopio University Hospital and University of Eastern Finland; and Department of Neurology (B.U.), Vasa Central Hospital, Finland.

出版信息

Neurology. 2019 Apr 2;92(14):e1600-e1609. doi: 10.1212/WNL.0000000000007246. Epub 2019 Mar 6.

DOI:10.1212/WNL.0000000000007246

PMID:30842289

Abstract

OBJECTIVE

To identify the genetic defect causing a distal calf myopathy with cores.

METHODS

Families with a genetically undetermined calf-predominant myopathy underwent detailed clinical evaluation, including EMG/nerve conduction studies, muscle biopsy, laboratory investigations, and muscle MRI. Next-generation sequencing and targeted Sanger sequencing were used to identify the causative genetic defect in each family.

RESULTS

A novel deletion-insertion mutation in ryanodine receptor 1 () was found in the proband of the index family and segregated with the disease in 6 affected relatives. Subsequently, we found 2 more families with a similar calf-predominant myopathy segregating with unique -mutated alleles. All patients showed a very slowly progressive myopathy without episodes of malignant hyperthermia or rhabdomyolysis. Muscle biopsy showed cores or core-like changes in all families.

CONCLUSIONS

Our findings expand the spectrum of -related disorders to include a calf-predominant myopathy with core pathology and autosomal dominant inheritance. Two families had unique and previously unreported mutations, while affected persons in the third family carried 2 previously known mutations in the same dominant allele.

摘要

目的

确定导致伴有内芯的远端小腿肌病的遗传缺陷。

方法

对遗传上未确定的以小腿为主的肌病的家族进行详细的临床评估，包括肌电图/神经传导研究、肌肉活检、实验室检查和肌肉 MRI。使用下一代测序和靶向 Sanger 测序来确定每个家族的致病遗传缺陷。

结果

在索引家族的先证者中发现了兰尼碱受体 1 () 的新型缺失-插入突变，该突变与 6 名受累亲属的疾病共分离。随后，我们发现了另外 2 个具有类似以小腿为主的肌病的家族，其与独特的 -突变等位基因共分离。所有患者均表现为进展非常缓慢的肌病，无恶性高热或横纹肌溶解症发作。肌肉活检显示所有家族均存在内芯或类似内芯的改变。