Mutations in TRPV4 are linked to a group of clinically distinct, but also overlapping axonal neuropathies, including Charcot–Marie–Tooth disease type 2C (CMT2C), scapuloperoneal spinal muscular atrophy, and congenital distal spinal muscular atrophy. The incidence of TRPV4-linked cases ranges from 0 to 7% in overall axonal neuropathy cohorts from European countries and Australia. However, the data from other areas remain largely unknown. In this study, we screened for TRPV4 mutations in a well-characterized USA cohort of 62 unrelated CMT2 patients without mutations in MFN2, GARS, NEFL, and GDAP1. All 15 coding exons of TRPV4 were analyzed by Sanger-sequencing. Clinical features of TRPV4-linked patients were compared with those lacking TRPV4 mutations. We identified two TRPV4 mutations in two patients. A TRPV4-R316C was identified in a patient with family history, while a TRPV4-R269C in an apparently sporadic case. Marked clinical variations were observed in the patients with TRPV4 mutations. Our data suggest that TRPV4-linked CMT2C accounts for a sizable fraction in this USA cohort of CMT2; it has a wide phenotypic spectrum, and vocal cord paralysis, scapular weakness and wasting, skeletal dysplasia, and hearing loss are suggestive signs for TRPV4-linked CMT2C.

中文翻译：

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TRPV4连锁的轴索性神经病在美国夏科特-玛丽-牙齿疾病2型队列中的发病率和临床特征。

TRPV4突变与一组临床上独特但又重叠的轴突神经病有关，包括2型Charcot-Marie-Tooth病（CMT2C），肩oper腹脊髓性肌萎缩症和先天性远端脊髓性肌萎缩症。在来自欧洲国家和澳大利亚的总体轴索神经病队列中，与TRPV4相关的病例的发病率范围为0％至7％。但是，其他地区的数据仍然未知。在这项研究中，我们筛选了一个特征明确的美国队列中62名无关的CMT2患者的TRPV4突变，这些患者在MFN2，GARS，NEFL和GDAP1中没有突变。TRPV4的所有15个编码外显子通过桑格测序分析。将TRPV4连锁患者的临床特征与缺乏TRPV4突变的患者进行比较。我们在两名患者中鉴定出两个TRPV4突变。在有家族史的患者中鉴定出TRPV4-R316C，而在明显散发的病例中鉴定出TRPV4-R269C。在具有TRPV4突变的患者中观察到明显的临床差异。我们的数据表明，与TRPV4连锁的CMT2C在这个美国CMT2队列中占了相当大的比例。它具有广泛的表型谱，声带麻痹，肩s无力和消瘦，骨骼发育异常和听力下降是TRPV4连锁的CMT2C的征兆。