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Table of Contents    
Year : 2018  |  Volume : 66  |  Issue : 2  |  Page : 528-529

Charcot Marie Tooth disease 2F and a novel mutation from India

Department of Neurology, P. D. Hinduja National Hospital and Research Centre, Mumbai, Maharashtra, India

Date of Web Publication15-Mar-2018

Correspondence Address:
Dr. Charulata S Sankhla
Department of Neurology, P. D. Hinduja National Hospital and Research Centre, Mumbai - 400 016, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.227317

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How to cite this article:
Ghodasara MK, Sankhla CS, Lovhale NS, Borse ST. Charcot Marie Tooth disease 2F and a novel mutation from India. Neurol India 2018;66:528-9

How to cite this URL:
Ghodasara MK, Sankhla CS, Lovhale NS, Borse ST. Charcot Marie Tooth disease 2F and a novel mutation from India. Neurol India [serial online] 2018 [cited 2020 Jun 7];66:528-9. Available from:


Charcot Marie Tooth (CMT) disease is a genetically heterogeneous group of inherited peripheral neuropathy. Mainly three types of CMT occur in adults; CMT1 [autosomal dominant (AD), demyelinating neuropathy], CMT2 (AD, rarely autosomal recessive, axonopathy), and CMTX (X-linked recessive, demyelinating). CMT3 and 4 occur early in childhood. CMT5 is a pure motor variety with an indolent course. Chakravarty et al.,[1] reported a family with clinical and electrophysiological profile with CMTX. Umesh et al.,[2] reported a case of CMT4C from India with SH3TC4 mutation.

We present a patient with an adult-onset CMT caused by heterozygous HSPB1 mutation encoding small heat shock protein 27 (Hsp27), which is seen in the CMT2F subtype.[3] The most common CMT2 is CMT2A (20%).[4] CMT2F is rare and the exact incidence is unknown.[4]

A 60-year old male patient presented with bilaterally symmetrical and progressive lower limb weakness and wasting since 4 years. He had a history of slippage of slippers and difficulty in pressing the accelerator and brake. He did not have a history of diurnal variation, proximal weakness, and sensory or autonomic involvement. He had a history of diabetes mellitus, which was well controlled on medication since the last 2 years. Other family members were also affected with the age of the youngest member at the onset of the disease being 35 years [Figure 1].
Figure 1: Family chart of the patient

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General examination revealed bilateral pes cavus. There were no thickened nerves. Central nervous system (CNS) examination revealed normal higher mental function and cranial nerves, as well as wasting and weakness of intrinsic muscles of hand and foot. Muscle power of dorsiflexors and planter flexors was 1/5 bilaterally. Power and tone in other muscle groups of all the limbs were normal. Deep tendon reflexes were normal except for absent ankle jerks. Both planter reflexes were absent. Cerebellar signs were absent. Superficial sensations were normal. Proprioception was impaired at the great toe; however, it was normal proximally and in the upper limbs. Romberg's was negative. Gait was of a high steppage type.

Clinically, a diagnosis of CMT was made with AD inheritance. Nerve conduction study was suggestive of motor more than sensory axonal peripheral neuropathy. Clinically and neurophysiologically, it was consistent with the diagnosis of CMT2. Genetic panel for CMT, done by targeted sequencing analysis, revealed a heterozygous missense variation in exon 2 of the HSPB1 gene (chr7:75933172; C>C/G), resulting in the amino acid substitution of glycine for arginine at codon 140 (p.R140G; ENST00000248553). This variant has not been reported in both the 1000 genomes and exome aggregation consortium (ExAC) databases. Pathogenic variants in HSPB1 were found in 4% of CMT2 cases in Italy.[5] Mutations in the gene encoding the 27 kDa small heat shock protein 27 (HSP27, also called heat shock 27 kD protein 1, HSPB1), have been shown to be causal in CMT2F (OMIM 606595) and distal hereditary motor neuropathy (dam) type II (OMIM 608634).[6] CMT2F is similar to distal hereditary motor neuropathy (HMN), except that there is no sensory loss in HMN.[7] As our patient had sensory involvement, it is consistent with the diagnosis of CMT2F instead of dHMN. Till date, six missense mutations (Arg127Trp, Arg136Trp, Ser135Phe, Thr151Ile, Pro182Ser, and Pro182Leu) have been discovered in families with dHMN or CMT2F.[7] The R140G variant is not reported in both the 1000 genomes and ExAC databases. This variant is predicted to be damaging by SIFT, LRT, and Mutation Taster and the region is conserved across species. Based on the above evidence, this HSPB1 variation can be classified as a probably significant variant.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Chakravarty A, Ghosh B, Sengupta S, Mukhopadhyay S. X-linked Charcot-Marie-Tooth disease with myokymia: Report of a family. Neurol India 2003;51:385-7.  Back to cited text no. 1
[PUBMED]  [Full text]  
Kalane UD, Datar C, Mahadevan A. First reported case of Charcot Marie Tooth disease type 4C in a child from India with SH3TC2 mutation but absent spinal deformities. Neurol India 2015;63:395-8.  Back to cited text no. 2
[PUBMED]  [Full text]  
Bird TD. Charcot Marie Tooth Hereditary Neuropathy. Overview Gene Reviews® NCBI Bookshelf. September 28, 1998; Last Revision: May 7, 2015.  Back to cited text no. 3
Bird TD. Charcot Marie Tooth Neuropathy Type 2. Overview Gene Reviews ® NCBI Bookshelf, Initial Posting: September 24, 1998; Last Revision: April 30, 2015.  Back to cited text no. 4
Capponi S, Geroldi A, Fossa P, Grandis M, Ciotti P, Gulli R, et al. HSPB1 and HSPB8 in inherited neuropathies: Study of an Italian cohort ofdHMN and CMT2 patients. J Peripher Nerv Syst 2011;16:287-94.  Back to cited text no. 5
Chung KW. Distal hereditary motor neuropathy in Korean patients with a small heat shock protein 27 mutation. Exp Mol Med 2008;40:304-12.  Back to cited text no. 6
Tang B, Liu X, Zhao G, Luo W, Xia K, Pan Q, et al. Mutation analysis of the small heat shock protein 27 gene in Chinese patients with Charcot Marie Tooth disease. Arch Neurol 2005;62:1201-7.  Back to cited text no. 7


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