Reports of spectrum of clinical manifestations in PMP22 gene–associated neuropathies (duplication/mutations) are scarce. To identify the frequency of PMP22 gene variations and establish their genotype-phenotype correlation. Patients with suspected genetic demyelinating neuropathy (n = 128) underwent evaluation for copy number variations and point mutations in PMP22 gene by multiplex ligation-dependent probe amplification (MLPA) and direct sequencing respectively. Of these, only 27 patients (M:F:19:8) from 18 families had PMP22 gene–associated neuropathy; they were subsequently analyzed for genotype-phenotype correlation. Twenty-five patients had PMP22 duplication while two patients had PMP22 missense mutations (p.A114V and p.L80P). Age at onset of neuropathy ranged from infancy to 63 years and symptom duration ranged from 2 to 32 years. Cranial nerve dysfunction in the form of ptosis, ophthalmoplegia, bifacial weakness, and sensorineural hearing loss was observed in addition to a number of systemic features. Three patients were asymptomatic. All except one patient were ambulant. Velocity of median nerve and amplitude of evoked motor responses from common peroneal nerve were significantly reduced in male patients. There was significantly worse disability in the late-onset group as compared with the early-onset group. Otherwise, the mean age at onset, frequency of skeletal deformities, patterns of motor weakness, muscle stretch reflexes, sensory impairment, disability rating scales, and electrophysiological parameters were comparable irrespective of gender, onset age, family history and ulnar nerve conduction velocities. The relatively low frequency of PMP22 duplication in the present cohort warrants a more comprehensive search to establish the genetic etiology. Further research into the role of other genetic variants as well as modifier genes and their effect on phenotypic heterogeneity is indicated.

中文翻译：

---

PMP22基因相关的神经病：来自印度的队列中的表型谱。

关于PMP22基因相关神经病变（重复/突变）的临床表现的光谱报道很少。以确定PMP22基因变异的频率，并建立其基因型与表型的相关性。怀疑患有遗传性脱髓鞘性神经病（n  = 128）的患者分别通过多重连接依赖性探针扩增（MLPA）和直接测序来评估PMP22基因的拷贝数变异和点突变。其中，来自18个家庭的27例患者（M：F：19：8）患有PMP22基因相关的神经病。随后对其进行基因型-表型相关性分析。25名患者患有PMP22两名患者患有PMP22时重复错义突变（p.A114V和p.L80P）。神经病发作的年龄范围从婴儿期到63岁，症状持续时间从2到32岁不等。除许多全身功能外，还观察到以上睑下垂，眼肌麻痹，双面无力和感觉神经性听力丧失等形式存在的颅神经功能障碍。3例无症状。除一名患者外，所有患者均为救护车。男性患者中位神经速度和腓总神经诱发的运动反应幅度明显降低。与早发组相比，晚发组的残疾明显更糟。否则，发病的平均年龄，骨骼畸形的频率，运动无力的模式，肌肉伸展反射，感觉障碍，残疾等级量表，不论性别，发病年龄，家族史和尺神经传导速度如何，电生理参数均具有可比性。频率相对较低在目前的队列中，PMP22重复值得进行更全面的研究以建立遗传病因。指示了对其他遗传变异以及修饰基因的作用及其对表型异质性影响的进一步研究。