Journal of Shanghai Jiao Tong University (Medical Science) ›› 2022, Vol. 42 ›› Issue (5): 609-616.doi: 10.3969/j.issn.1674-8115.2022.05.008

• Clinical research • Previous Articles     Next Articles

Analysis of genetic and clinical characteristics of PMP22-associated peripheral neuropathy

ZHU Xiaowei1,2(), ZHAN Feixia1, ZHANG Chao2, LIU Shihua2, ZHONG Ping2, CAO Li1,2, LUAN Xinghua1,2()   

  1. 1.Department of Neurology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
    2.Department of Neurology, Suzhou Hospital of Anhui Medical University, Suzhou 234000, China
  • Received:2021-12-06 Accepted:2022-05-06 Online:2022-05-28 Published:2022-05-28
  • Contact: LUAN Xinghua;
  • Supported by:
    National Natural Science Foundation of China(81870889)

Abstract: Objective

·To investigate the genetic and clinical features of peripheral neuropathy patients with PMP22 gene variations and the association between genotype and clinical phenotype.


·A total of 162 patients with peripheral neuropathy who were treated in Department of Neurology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine from 2006 to 2022 were collected. Molecular detecting techniques including combining multiplex ligation-dependent probe amplification (MLPA), whole exon sequencing (WES) and Sanger sequencing were used to comprehensively analyze the genetic variation of 162 patients, and 26 probands with PMP22 gene variations and their 33 family members were screened out. The genetic variations included duplication, deletion and point mutations. The clinical and genetic characteristics of 26 patients with PMP22-associated peripheral neuropathy were further analyzed. The clinical characteristics included clinical demographic data, clinical manifestations, electrophysiological and pathological characteristics.


·There were a total of 59 (37 male and 22 female) individuals with PMP22-associated peripheral neuropathy, among whom 46 patients in 13 families had positive family histories and 13 did not. The median age at onset of neuropathy was 34.0 (14.0, 49.5) years old. The initial symptom was limb weakness or limb numbness. There were 51 Charcot-Marie-Tooth type-1A (CMT1A) patients with PMP22 duplication, 6 hereditary neuropathy with liability to pressure palsies (HNPP) patients with PMP22 deletion and 2 Dejerine-Sottas syndrome (DSS) patients with PMP22 point mutations (p.S72L and p.G100V). Sixteen patients underwent electrophysiological detections. Compared with the 4 PMP22 deletion patients, the motor nerve conduction velocity (MCV), compound muscle action potential (CMAP) and sensory nerve conduction velocities (SCV) of 12 PMP22 duplication patients were obviously decreased (all P<0.05). Conduction block was found in both kinds of mutation types. Sural nerve biopsies were performed in 12 patients, including 8 PMP22 duplication, 3 PMP22 deletion and 1 PMP22 point mutation, and pathological changes such as thinning of myelinated nerve fibers, “onion bulbs” and decreased nerve fiber density were observed in varying degrees.


·PMP22 gene-associated neuropathies can be characterized by CMT1A, HNPP and DSS with high clinical heterogeneity. Patients with demyelinating manifestations on electrophysiological detections and sural nerve biopsy need genetic testing for PMP22 gene duplication, deletion and point mutation after ruling out acquired etiology. It is available to help optimize diagnosis and genetic counseling of the disease.

Key words: Charcot-Marie-Tooth type-1A (CMT1A), hereditary neuropathy with liability to pressure palsies (HNPP), Dejerine-Sottas syndrome (DSS), PMP22 gene, mutation

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