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首页> 外文期刊>BMC Medical Genomics >Bi-allelic variants in MTMR5/SBF1 cause Charcot-Marie-Tooth type 4B3 featuring mitochondrial dysfunction
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Bi-allelic variants in MTMR5/SBF1 cause Charcot-Marie-Tooth type 4B3 featuring mitochondrial dysfunction

机译：MTMR5 / SBF1中的双级等位基因变体导致Charcot-Marie-Tooth型4B3，具有线粒体功能障碍

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Charcot-Marie-Tooth disease (CMT) type 4B3 (CMT4B3) is a rare form of genetic neuropathy associated with variants in the MTMR5/SBF1 gene. MTMR5/SBF1 is a pseudophosphatase predicted to regulate endo-lysosomal trafficking in tandem with other MTMRs. Although almost ubiquitously expressed, pathogenic variants primarily impact on the peripheral nervous system, corroborating the involvement of MTMR5/SBF1 and its molecular partners in Schwann cells-mediated myelinization. We report a case of severe CMT4B3 characterized by early-onset motor and axonal polyneuropathy in an Italian child in absence of any evidence of brain and spine MRI abnormalities or intellectual disability and with a biochemical profile suggestive of mitochondrial disease. Using an integrated approach combining both NGS gene panels and WES analysis, we identified two novel compound heterozygous missense variants in MTMR5/SBF1 gene, p.R763H (c.2291G??A) and p.G1064E (c.3194G??A). Studies in muscle identified partial defects of oxidative metabolism. We describe the first case of an early onset severe polyneuropathy with motor and axonal involvement, due to recessive variants in the MTMR5/SBF1 gene, with no evidence of brain and spine MRI abnormalities, intellectual disability, no clinical and neurophysiological evidences of distal sensory impairment, and rapid neuromuscular deterioration. This report suggests that MTMR5/SBF1 should be considered in cases of infantile-onset CMT with secondary mitochondrial dysfunction.
机译：Charcot-Marie-Doother疾病（CMT）4B3（CMT4B3）是一种罕见的遗传神经病变，与MTMR5 / SBF1基因中的变体相关联。 MTMR5 / SBF1是假磷酸酶预测，以调节与其他MTMRS串联的末端溶酶体贩运。虽然几乎普遍地表达了致病变异，主要对外周神经系统产生影响，证实了MTMR5 / SBF1及其分子伴侣在施旺细胞的介导的髓鞘中的累积。我们报告了一种严重的CMT4B3，其特征在于意大利儿童早上发病马达和轴突多肌病，缺乏任何脑和脊柱MRI异常或智力残疾的证据，以及暗示线粒体疾病的生化型材。使用组合NGS基因面板和WES分析的综合方法，我们在MTMR5 / SBF1基因中鉴定了两种新化合物杂合物畸形变体，P.R763H（C.2291G≤αa）和p.G1064E（C.3194G？＆gt ;？一个）。肌肉的研究确定了氧化代谢的部分缺陷。通过MTMR5 / SBF1基因的隐性变体，描述了具有电动机和轴突累积的早期发病严重多发性病变的第一种情况，没有脑和脊柱MRI异常，智力残疾，无临床和神经生理学障碍的证据，无临床和神经生理证据，快速神经肌肉劣化。本报告表明，在具有二次线粒体功能障碍的婴儿发作CMT的情况下，应考虑MTMR5 / SBF1。

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