Laboratory of Inflammatory Myopathies, Division of Rheumatology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Laboratory of Molecular and Cellular Biology, Department of Neurology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Clin Rheumatol. 2018 Apr;37(4):1129-1136. doi: 10.1007/s10067-017-3913-1. Epub 2017 Nov 10.
The objective of this study is to report a Brazilian patient and his family with inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD). A systematic review of the literature on the valosin-containing protein (VCP) mutation was also performed. The proband (patient) was initially treated as a case of possible refractory polymyositis with Paget's disease and later as an inclusion body myopathy. However, after admission to our service, and considering his personal and familial antecedents, whole exome sequencing was performed revealing valosin-containing protein (VCP) c.290G>A (p.Gly97Glu) mutation in the patient and his nine family members. The clinical presentation of the patient and his family was characterized by different degrees and evaluations of IBMPFD. According to the literature, only one family (Chinese) has this same VCP mutation concomitantly with different IBMPFD phenotype manifestations. The present study shows that IBMPFD should be considered as a differential diagnosis in patients with inflammatory myopathies associated to bone disease and/or cognitive impairment. Moreover, the study expands the genotypic spectrum of missense mutations of VCP gene in a Brazilian family with variable phenotypes.
本研究旨在报告一例巴西患者及其家族，该患者患有伴有骨 Paget 病和额颞叶痴呆的包涵体肌病（IBMPFD）。还对包含伏隔核蛋白（VCP）突变的文献进行了系统回顾。先将先证者（患者）初诊为可能难治性多发性肌炎伴 Paget 病，后来又诊断为包涵体肌病。然而，在收入我院后，考虑到他的个人和家族病史，对其进行了外显子组测序，发现患者及其 9 名家族成员存在伏隔核蛋白（VCP）c.290G>A（p.Gly97Glu）突变。患者及其家族的临床表现特征为不同程度和不同 IBMPFD 表现的包涵体肌病。根据文献，仅有一个家族（中国）存在相同的 VCP 突变，同时伴有不同的 IBMPFD 表型表现。本研究表明，对于伴有骨病和/或认知障碍的炎性肌病患者，应考虑将 IBMPFD 作为鉴别诊断。此外，该研究还扩展了具有不同表型的巴西家族中 VCP 基因突变的基因型谱。
