Department of Clinical Development, Translational Medical Center, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan Department of Neuromuscular Research, National Institute of Neuroscience, NCNP, Tokyo, Japan Department of Education, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
Department of Clinical Development, Translational Medical Center, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan Department of Neuromuscular Research, National Institute of Neuroscience, NCNP, Tokyo, Japan Department of Neurophysiology, Tokyo Medical University, Tokyo, Japan.
J Neurol Neurosurg Psychiatry. 2015 May;86(5):483-9. doi: 10.1136/jnnp-2014-309009. Epub 2014 Sep 24.
In hereditary myopathy with early respiratory failure (HMERF), cytoplasmic bodies (CBs) are often localised in subsarcolemmal regions, with necklace-like alignment (necklace CBs), in muscle fibres although their sensitivity and specificity are unknown.
To elucidate the diagnostic value of the necklace CBs in the pathological diagnosis of HMERF among myofibrillar myopathies (MFMs).
We sequenced the exon 343 of TTN gene (based on ENST00000589042), which encodes the fibronectin-3 (FN3) 119 domain of the A-band and is a mutational hot spot for HMERF, in genomic DNA from 187 patients from 175 unrelated families who were pathologically diagnosed as MFM. We assessed the sensitivity and specificity of the necklace CBs for HMERF by re-evaluating the muscle pathology of our patients with MFM.
TTN mutations were identified in 17 patients from 14 families, whose phenotypes were consistent with HMERF. Among them, 14 patients had necklace CBs. In contrast, none of other patients with MFM had necklace CBs except for one patient with reducing body myopathy. The sensitivity and specificity were 82% and 99%, respectively. Positive predictive value was 93% in the MFM cohort.
The necklace CB is a useful diagnostic marker for HMERF. When muscle pathology shows necklace CBs, sequencing the FN3 119 domain of A-band in TTN should be considered.
在遗传性肌病伴早期呼吸衰竭（HMERF）中，细胞质小体（CBs）通常定位于肌纤维的肌小节下区域，呈项链状排列（项链 CBs），但其敏感性和特异性尚不清楚。
阐明项链 CBs 在肌原纤维肌病（MFMs）中 HMERF 的病理诊断中的诊断价值。
我们对 175 个无关家系的 187 名患者的基因组 DNA 进行了 TTN 基因外显子 343 测序（基于 ENST00000589042），该基因编码 A 带的纤连蛋白-3（FN3）119 结构域，是 HMERF 的突变热点。我们通过重新评估这些具有 MFMs 患者的肌肉病理学，评估了项链 CBs 对 HMERF 的敏感性和特异性。
在 14 个家系的 17 名患者中发现了 TTN 突变，其表型与 HMERF 一致。其中 14 名患者有项链 CBs。相比之下，除了一名患有进行性肌营养不良症的患者外，其他 MFMs 患者均无项链 CBs。敏感性和特异性分别为 82%和 99%。在 MFMs 队列中，阳性预测值为 93%。
项链 CBs 是 HMERF 的有用诊断标志物。当肌肉病理学显示项链 CBs 时，应考虑在 TTN 中对 A 带的 FN3 119 结构域进行测序。
