Ma Xinran, Liu Xiaoxuan, Duan Xiaohui, Fan Dongsheng
Department of Neurology, Peking University Third Hospital, Beijing, China.
Key Laboratory for Neuroscience, National Health Commission/Ministry of Education, Peking University, Beijing, China.
Front Neurol. 2023 Jul 4;14:1148044. doi: 10.3389/fneur.2023.1148044. eCollection 2023.
Periaxins (encoded by ) play an important role in the stabilization of peripheral nerve myelin. Mutations in can lead to Charcot-Marie-Tooth disease type 4F (CMT4F).
In this study, we screened for mutations using next-generation sequencing and whole-exome sequencing in a large Chinese CMT cohort consisting of 465 unrelated index patients and 650 healthy controls. Sanger sequencing was used for the validation of all identified variants. We also reviewed all previously reported -related CMT cases and summarized the clinical manifestations and genetic features of -related CMTs.
The hit rate for biallelic variants in our cohort of Chinese CMT patients was 0.43% (2/465). One patient carried a previously unreported splice-site mutation (c.25_27 + 9del) compound heterozygous with a known nonsense variant. Compiling data on CMT4F cases and variants from the medical literature confirmed that early-onset (95.2%), distal amyotrophy or weakness (94.0%), feet deformity (75.0%), sensory impairment or sensory ataxia (65.5%), delayed motor milestones (60.7%), and spinal deformity (59.5%) are typical features for CMT4F. Less frequent features were auditory impairments, respiratory symptoms, late onset, dysarthria or hoarseness, ophthalmic problems, and central nervous system involvement. The two cases with biallelic missense mutations have later onset age than those with nonsense or frameshift mutations. We did not note clear correlations between the type and site of mutations and clinical severity or distinct constellations of symptoms.
Consistent with observations in other countries and ethnic groups, -related CMT is rare in China. The clinical spectrum is wider than previously anticipated.
外周髓鞘蛋白（由 编码）在周围神经髓鞘的稳定中起重要作用。 中的突变可导致4F型遗传性运动感觉神经病（CMT4F）。
在本研究中，我们在一个由465例无亲缘关系的索引患者和650例健康对照组成的大型中国CMT队列中，使用二代测序和全外显子组测序筛选 突变。采用桑格测序法验证所有鉴定出的变异。我们还回顾了所有先前报道的与 相关的CMT病例，并总结了与 相关的CMT的临床表现和遗传特征。
在我们的中国CMT患者队列中，双等位基因 变异的检出率为0.43%（2/465）。一名患者携带一个先前未报道的剪接位点突变（c.25_27 + 9del），与一个已知的无义变异构成复合杂合子。汇总医学文献中CMT4F病例和 变异的数据证实，早发型（95.2%）、远端肌萎缩或无力（94.0%）、足部畸形（75.0%）、感觉障碍或感觉性共济失调（65.5%）、运动发育迟缓（60.7%）和脊柱畸形（59.5%）是CMT4F的典型特征。不太常见的特征是听觉障碍、呼吸道症状、晚发型、构音障碍或声音嘶哑、眼科问题和中枢神经系统受累。两例双等位基因错义突变患者的起病年龄比无义或移码突变患者晚。我们没有发现突变类型和位点与临床严重程度或不同症状组合之间存在明显相关性。
与其他国家和种族群体的观察结果一致，与 相关的CMT在中国很少见。临床谱比先前预期的更广泛。
