GJB1 Mutation-A Disease Spectrum: Report of Case Series.

Jingwen Niu,Yi Li,Liri Jin,Yi Dai,Liying Cui,Mingsheng Liu,Qingyun Ding,Yuzhou Guan

doi:10.3389/fneur.2019.01406

Abstract

Introduction: Patients with GJB1 mutations manifested as pure central nervous system (CNS) involvement without peripheral neuropathy have not been adequately reported. To expand the disease spectrum of GJB1 mutations, we report a case series.Methods: Eleven patients from 9 families with GJB1 mutations were reviewed. The clinical manifestations, electrophysiological studies, and gene tests were summarized.Results: Nine patients had peripheral neuropathy, one patient had both peripheral neuropathy and mild cognitive impairment, and one patient had recurrent episodic limbs weakness and aphasia with normal electrophysiological study, indicating CNS involvement only.Discussion: GJB1 mutations form a clinical spectrum, including most patients with peripheral nerve involvement, those with both peripheral neuropathy and CNS involvement, and patients with CNS involvement only.

Highlights

Patients with GJB1 mutations manifested as pure central nervous system (CNS) involvement without peripheral neuropathy have not been adequately reported
One patient (Patient 1) had both peripheral neuropathy and possibly CNS involvement manifested as mild cognitive impairment
DNA analysis showed a thymine to cytosine transition sequence alteration in the connexin 32 (Cx32) allele of GJB1 gene in nucleotide position 113 predicting a valine to alanine amino acid substitution at codon position 38. It is well-established that in addition to the typical peripheral features of CMT, CNS involvement could be observed in patients with X-linked Charcot-Marie-Tooth disease type 1 (CMTX1)

Summary

Introduction

Patients with GJB1 mutations manifested as pure central nervous system (CNS) involvement without peripheral neuropathy have not been adequately reported. To expand the disease spectrum of GJB1 mutations, we report a case series. X-linked Charcot-Marie-Tooth disease type 1 (CMTX1), the second most common cause of hereditary neuropathy, is caused by mutations in GJB1, which codes for connexin 32 (Cx32). Cx32 is expressed in the myelinating Schwann cell of peripheral nerves, as well as the outer oligodendrocyte membranes in the central nervous system (CNS) [1]. GJB1 mutation usually causes a progressive sensorimotor neuropathy, CMTX1. We describe serial cases of GJB1 mutation which form a clinical spectrum, including most patients with only peripheral nerve involvement, patient with both peripheral neuropathy and CNS involvement, and patient with only CNS involvement

Methods

Results

Conclusion