Voermans N C, Guillard M, Doedée R, Lammens M, Huizing M, Padberg G W, Wevers R A, van Engelen B G, Lefeber D J
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Clin Neuropathol. 2010 Mar-Apr;29(2):71-7.
We present a comprehensive report of two siblings with hereditary inclusion body myopathy (HIBM). The clinical features and histological characteristics of the muscle biopsies showed the typical pattern of predominantly distal vacuolar myopathy with quadriceps sparing. This was confirmed by muscle MRI. PNA lectin staining showed an increased signal at the sarcolemma in patient muscle sections compared to control muscle, indicating reduced sialylation of glycoconjugates. Mutation analysis revealed compound heterozygous mutations in the GNE gene, encoding the key enzyme in sialic acid synthesis UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase: a missense mutation (c.2086G > A; p.V696M) previously described in HIBM patients of Indian origin, and a novel frame shift mutation (c.1295delA; p.K432RfsX17) leading to a premature stopcodon. These findings confirmed the diagnosis of HIBM on the histological, molecular and biochemical level.
我们报告了两例患有遗传性包涵体肌病（HIBM）的兄弟姐妹的综合情况。肌肉活检的临床特征和组织学特征显示出典型模式，主要为远端空泡性肌病，股四头肌未受累。肌肉MRI证实了这一点。与对照肌肉相比，PNA凝集素染色显示患者肌肉切片肌膜处信号增强，表明糖缀合物的唾液酸化减少。突变分析揭示了GNE基因中的复合杂合突变，该基因编码唾液酸合成中的关键酶UDP-N-乙酰葡糖胺2-表异构酶/N-乙酰甘露糖胺激酶：一个先前在印度裔HIBM患者中描述过的错义突变（c.2086G > A；p.V696M），以及一个导致过早终止密码子的新型移码突变（c.1295delA；p.K432RfsX17）。这些发现从组织学、分子和生化水平上证实了HIBM的诊断。
