Abstract：
Mutations in the valosin-containing protein (VCP) gene cause autosomal dominant multisystem proteinopathy 1 (MSP1), characterized by a variable combination of inclusion body myopathy (IBM), Paget\'s disease of bone (PDB), and frontotemporal dementia (FTD). Here we report a novel VCP missense mutations in an Italian family with FTD as the prevalent manifestation and compare our results with those described in the literature.
We described the clinical, molecular, and imaging data of the studied family. We also conducted a systematic literature search with the aim of comparing our findings with previously reported VCP-related phenotypes.
A novel heterozygous VCP missense mutation (c 0.473 T > C/p.Met158Thr) was found in all the affected family members. The proband is a 69-year-old man affected by progressive muscle weakness since the age of 49. Muscle MRI showed patchy fatty infiltration in most muscles, and STIR sequences revealed an unusual signal increase in distal leg muscles. At age 65, he presented a cognitive disorder suggestive of behavioral variant FTD. A bone scintigraphy also revealed PDB. The patient\'s mother, his maternal aunt and her daughter had died following a history of cognitive deterioration consistent with FTD; the mother also had PDB. No relatives had any muscular impairments. Reviewing the literature data, we observed a different sex distribution of VCP-related phenotypes, being FTD prevalence higher among women as compared to men (51.2 % vs 31.2 %) and IBM prevalence higher among men as compared to women (92.1 % vs 72.8 %).
This study broadened our clinical, genetic, and imaging knowledge of VCP-related disorders.
We described the clinical, molecular, and imaging data of the studied family. We also conducted a systematic literature search with the aim of comparing our findings with previously reported VCP-related phenotypes.
A novel heterozygous VCP missense mutation (c 0.473 T > C/p.Met158Thr) was found in all the affected family members. The proband is a 69-year-old man affected by progressive muscle weakness since the age of 49. Muscle MRI showed patchy fatty infiltration in most muscles, and STIR sequences revealed an unusual signal increase in distal leg muscles. At age 65, he presented a cognitive disorder suggestive of behavioral variant FTD. A bone scintigraphy also revealed PDB. The patient\'s mother, his maternal aunt and her daughter had died following a history of cognitive deterioration consistent with FTD; the mother also had PDB. No relatives had any muscular impairments. Reviewing the literature data, we observed a different sex distribution of VCP-related phenotypes, being FTD prevalence higher among women as compared to men (51.2 % vs 31.2 %) and IBM prevalence higher among men as compared to women (92.1 % vs 72.8 %).
This study broadened our clinical, genetic, and imaging knowledge of VCP-related disorders.
摘要：
目的：含valosin蛋白（VCP）基因的突变导致常染色体显性遗传多系统蛋白病1（MSP1），以包涵体肌病(IBM)的可变组合为特征，佩吉特骨病（PDB），额颞叶痴呆（FTD）。在这里，我们报告了一个以FTD为普遍表现的意大利家族中的新型VCP错义突变，并将我们的结果与文献中描述的结果进行了比较。
方法：我们描述了临床，分子，和所研究家庭的影像数据。我们还进行了系统的文献检索，目的是将我们的发现与以前报道的VCP相关表型进行比较。
结果：一种新的杂合VCP错义突变（c0.473T>C/p。在所有受影响的家庭成员中都发现了Met158Thr）。先证者是一名69岁的男性，自49岁以来就受到进行性肌肉无力的影响。肌肉MRI显示大部分肌肉有斑片状脂肪浸润，和STIR序列显示腿部远端肌肉异常信号增加。65岁时，他出现了一种认知障碍，提示行为变异FTD。骨闪烁显像也显示PDB。病人的母亲，他的姑姑和她的女儿因认知恶化的病史与FTD一致而死亡;母亲也患有PDB。没有亲属有任何肌肉损伤。回顾文献数据，我们观察到VCP相关表型的性别分布不同，女性FTD患病率高于男性（51.2%vs31.2%），男性IBM患病率高于女性（92.1%vs72.8%）。
结论：这项研究扩大了我们的临床，遗传,VCP相关疾病的影像学知识。
方法：我们描述了临床，分子，和所研究家庭的影像数据。我们还进行了系统的文献检索，目的是将我们的发现与以前报道的VCP相关表型进行比较。
结果：一种新的杂合VCP错义突变（c0.473T>C/p。在所有受影响的家庭成员中都发现了Met158Thr）。先证者是一名69岁的男性，自49岁以来就受到进行性肌肉无力的影响。肌肉MRI显示大部分肌肉有斑片状脂肪浸润，和STIR序列显示腿部远端肌肉异常信号增加。65岁时，他出现了一种认知障碍，提示行为变异FTD。骨闪烁显像也显示PDB。病人的母亲，他的姑姑和她的女儿因认知恶化的病史与FTD一致而死亡;母亲也患有PDB。没有亲属有任何肌肉损伤。回顾文献数据，我们观察到VCP相关表型的性别分布不同，女性FTD患病率高于男性（51.2%vs31.2%），男性IBM患病率高于女性（92.1%vs72.8%）。
结论：这项研究扩大了我们的临床，遗传,VCP相关疾病的影像学知识。
