Recessive GNE Mutations in Korean Nonaka Distal Myopathy Patients with or without Peripheral Neuropathy.

Autosomal recessive Nonaka distal myopathy is a rare autosomal recessive genetic disease characterized by progressive degeneration of the distal muscles, causing muscle weakness and decreased grip strength. It is primarily associated with mutations in the GNE gene, which encodes a key enzyme of sialic acid biosynthesis (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase). This study was performed to find GNE mutations in six independent distal myopathy patients with or without peripheral neuropathy using whole-exome sequencing (WES). In silico pathogenic prediction and simulation of 3D structural changes were performed for the mutant GNE proteins. As a result, we identified five pathogenic or likely pathogenic missense variants: c.86T>C (p.Met29Thr), c.527A>T (p.Asp176Val), c.782T>C (p.Met261Thr), c.1714G>C (p.Val572Leu), and c.1771G>A (p.Ala591Thr). Five affected individuals showed compound heterozygous mutations, while only one patient revealed a homozygous mutation. Two patients revealed unreported combinations of combined heterozygous mutations. We observed some specific clinical features, such as complex phenotypes of distal myopathy with distal hereditary peripheral neuropathy, an earlier onset of weakness in legs than that of hands, and clinical heterogeneity between two patients with the same set of compound heterozygous mutations. Our findings on these genetic causes expand the clinical spectrum associated with the GNE mutations and can help prepare therapeutic strategies.

Smartphone-assimilated colorimetric sensor for sub-nanomolar emamectin detection via KA30 capped silver nanoparticles in food, bio-fluids and water samples.

In this report, we firstly synthesized nitro calix [4] resorcinarene compound (referred as KA30) and characterized it though proton (1H) nuclear magnetic resonance (NMR) spectroscopy, electrospray ionization mass spectrometry (ESI-MS) and Fourier Transform Infra-red (FTIR) spectroscopy. KA30 was applied as functionalizing agent for the formation of silver nanoparticles (KA30-AgNPs). These NPs were confirmed as highly selective and extremely sensitive colorimetric sensor for ultra-low level detection of emamectin (EMA) as a novel report. Significant aspect of the sensor is its unique detection range between 0.0005 and 29.5 µM via color change from yellow to colorless with hypochromic-bathochromic shift exhibiting limit of detection (LOD) and limit of quantification (LOQ) as 0.12 nM and 0.4 nM respectively. The sensor was applied to colorimetrically and optically detect EMA in real samples of serum, urine and food. The sensor was further allied with smartphone for real-time, and on-site detection of EMA and results were validated through UPLC.

Mutational screening of GDAP1 in dysphonia associated with Charcot-Marie-Tooth disease: clinical insights and phenotypic effects.

INTRODUCTION: Mutations in GDAP1 (Ganglioside-induced differentiation-associated protein 1) gene are linked to Charcot-Marie-Tooth disease (CMT), a Heterogenous group of disorders with multiple phenotypes, characterized by peripheral nerve dysfunction that can lead to vocal cord paralysis and diaphragmatic dysfunction. MAIN BODY: All three affected children of this chosen family have manifested the same clinical symptoms with progressive weakness, mild sensory impairment, and absent tendon reflexes in their early years. Electrodiagnostic analysis displayed an axonal type of neuropathy in affected patients. Sequencing of the GDAP1 gene was requested for all members of the family. Diagnostic assessments included pulmonary and vocal cord function tests, as well as phrenic and peripheral nerve conduction studies. Pathogenicity of GDAP1 variant p.Pro419Leu with axonal CMT2 and autosomal recessive inheritance was confirmed via in silico analysis. Patients with GDAP1 mutations showed dysphonia, speech difficulties, and the characteristic symptoms of CMT. The severity of symptoms correlated with the presence of a type of GDAP1 mutation. Patients with normal vocal cords and pulmonary function exhibited milder symptoms compared to those with GDAP1 mutations. Our study provides clinical insights into the phenotypic effects of GDAP1 mutations in CMT patients. The findings highlight the adverse clinical course and severe disability associated with GDAP1 mutations, including weak limb and laryngeal muscles. CONCLUSION: Patients with GDAP1 mutations and autosomal recessive neuropathy present with dysphonia and require interventions such as surgery, braces, physical therapy, and exercise. Early diagnosis and comprehensive clinical evaluations are crucial for managing CMT patients with GDAP1 mutations.

Loneliness and mental health related impacts of COVID-19: a narrative review.

Loneliness is the one of the common phase experienced during COVID-19 pandemic. It has impacted mental health of all ages specifically children and adolescents. The aim of this review was to assess level of loneliness and mental health related impacts of COVID-19 among both; children and adolescents. For this literature review, two independent reviewers searched articles on Cochrane library, MEDLINE, Google Scholar and Science-direct. Both MeSH terms and free text terms were used for search purposes between December 01, 2019 and December 30, 2021. A total of 14 studies met inclusion criteria and of these, 8 studies were related to mental health related impacts of COVID-19 pandemic whereas 6 studies involved both aspects i.e. loneliness and mental health among children and adolescents. One study was qualitative, one interventional, and remaining 12 were cross-sectional surveys. The findings of this review suggest an increase in level of loneliness and mental health related impacts during COVID-19 pandemic among children and adolescents. Loneliness, social distancing and internet usage therefore re strongly correlated with mental health related issues including stress, anxiety and depression.

Biallelic mutations in pakistani families with autosomal recessive prelingual nonsyndromic hearing loss.

BACKGROUND: Nonsyndromic autosomal recessive hearing loss (DFNB) is an etiologically heterogeneous disorder group showing a wide spectrum of onset ages and severity. DFNB genes are very diverse in their types and functions, making molecular diagnosis difficult. DFNB is particularly frequent in Pakistan, which may be partly due to consanguinity. OBJECTIVE: This study was performed to determine the genetic causes in Pakistani DFNB families with prelingual onset and to establish genotype-phenotype correlation. METHODS: Whole exome sequencing and subsequent genetic analysis were performed for 11 Pakistani DFNB families including eight consanguineous families. RESULTS: We identified eight pathogenic or likely pathogenic mutations in LOXHD1, GJB2, SLC26A4, MYO15A, and TMC1 from six families. The GJB2 mutations were identified in two families each with compound heterozygous mutations and a homozygous mutation. The compound heterozygous mutations in LOXHD1 ([p.D278Y] + [p.D1219E]) and GJB2 [p.M1?] + [p.G12Vfs*2]) were novel. The four missense or start-loss mutations were located at well conserved residues, and most in silico analysis predicted their pathogenicity. In addition to causative mutations, we found compound heterozygous mutations in PTPRQ as variants of uncertain significance. CONCLUSION: This study identified biallelic mutations as the underlying cause of early onset DFNB in six Pakistani families. This study will be helpful in providing an exact molecular diagnosis and treatment of prelingual onset deafness patients.

Neuroprotective effects of 2-(2-thienyl) benzothiazoline on gross motor skill deficits in rotenone induced rat model of Parkinson's disease.

In elderly aged people, Parkinson's disease is reported as 2nd most prevailing neuro-degenerative disease. Presently benzothiazole derivatives are gaining attention after showing positive results in various animal models for the investigation of different motor-diseases. In Current work, the 2- (2 Thienyl)Benzothiazoline is synthesized and its therapeutic effect was evaluated against rotenone-induced Parkinson's disease. It was expected to obtain the positive results in the treatment because thiophen group has been successfully reported in various literature as effective agent in the treatment of cognitive and locomotory disease. So, we used a Parkinson's inducive compound rotenone and injectedit intraperitoneally. The dose that we were used was 1.5mg/kg and treatment proceeded for 8 days in rats as rotenone inhibit the functioning of mitochondrial complex I. Administration of 2- (2 Thienyl)Benzothiazoline (10mg/kg per day) was already started 15 days prior to rotenone dose injection. The effects of both pre-treatment and without pre-treatment of 2- (2 Thienyl)Benzothiazoline were assessed by the use of various motor parameters of behavior such as pole test and Kondziela's inverted screen test for checking muscular strength, whereas inclined plane test, open field test and Rota rod test for motor coordination. Pre-treatment with drug reversed the gross motor impairments which were produced by rotenone. We conclude that 2- (2 Thienyl)Benzothiazoline, like its other candidate drug also protects against destructive effects of the compound rotenone and itcan be used as beneficial drug against various neurodegenerative diseases.

Prevalence of Risk Factors of the Female Athlete Triad among Young Elite Athletes of Pakistan.

BACKGROUND: Female athletes who are not vigilant about their food choices and choose extraneous physical activities may head towards negative health effects. PURPOSE: The purpose was to determine the prevalence of risk factors that may lead to the Female Athlete Triad among young elite athletes in Pakistan. STUDY DESIGN & METHODS: A cross sectional questionnaire-based study was conducted in 2018 at Pakistan Sports Board to investigate the risk factors of The Female Athlete Triad among young elite athletes based in national training camps of major metropolitan cities. Trained and professional female elite athletes of age 18 - 25 years, able to comprehend questionnaire in English were included. Athletes completed the questionnaire including demographics, educational qualifications, Body Mass Index, sports participation, and playing hours. The Eating Aptitude Test-26 (EAT-26) and questionnaires on risks of amenorrhea and risks of low bone mineral density were completed. Individual prevalence of the risk factors of three components was assessed. The data were analyzed using SPSS-20 and descriptive statistics applied. RESULTS: A sample of 60 elite athletes, (23.57 + 2.37 years, BMI 21.97 +1.90) who participated in various sports were included. EAT-26 results indicated that 50% of athletes were at risk of an eating disorder. Disordered Eating behaviors in need of referral were identified in 83.3%. Risks for amenorrhea were identified in 15%, and concerning low Bone Mineral Density, no risks were identified, except the intake of caffeinated beverages in 51.7%. CONCLUSION: The prevalence of risk for disordered eating was found to be significant among female elite athletes of Pakistan, but risk of amenorrhea and low bone mineral density were not of major concern. LEVEL OF EVIDENCE: 3b.

Prediction and evaluation of multi epitope based sub-unit vaccine against Salmonella typhimurium.

Salmonella enteric serovar Typhimurium is the most common enteric pathogen in humans and animals. Consumption of contaminated food or water triggers inflammation that allows Salmonella to spread into the gut and causes gastrointestinal diseases. The infection spreads by intestinal invasion, phagocyte internalization and subsequent dissemination in many other patients. This research used TolA, a Salmonella typhimurium membrane protein, to computationally design a multi-epitope vaccine against the pathogen. Complete consistency of the candidate vaccine was checked In silico, and molecular dynamics simulations confirmed the vaccine's stability. According to docking report, the vaccine has a good affinity with toll-like receptors. In silico cloning and codon optimization techniques improved the vaccine's efficacy in Salmonella typhimurium manifestation process. The candidate vaccine induced an efficient immune response, as determined by In silico immune simulation. Computational studies revealed that the engineered multi-epitope vaccine is structurally stable, capable of eliciting particular immunological reactions, and therefore a candidate for a latent Salmonella typhimurium vaccine. However, wet lab studies and further investigations are required to confirm the results.

Novel homozygous mutations in Pakistani families with Charcot-Marie-Tooth disease.

BACKGROUND: Charcot-Marie-Tooth disease (CMT) is a group of genetically and clinically heterogeneous peripheral nervous system disorders. Few studies have identified genetic causes of CMT in the Pakistani patients. METHODS: This study was performed to identify pathogenic mutations in five consanguineous Pakistani CMT families negative for PMP22 duplication. Genomic screening was performed by application of whole exome sequencing. RESULTS: We identified five pathogenic or likely pathogenic homozygous mutations in four genes: c.2599C > T (p.Gln867*) and c.3650G > A (p.Gly1217Asp) in SH3TC2, c.19C > T (p.Arg7*) in HK1, c.247delG (p.Gly83Alafs*44) in REEP1, and c.334G > A (p.Val112Met) in MFN2. These mutations have not been reported in CMT patients. Mutations in SH3TC2, HK1, REEP1, and MFN2 have been reported to be associated with CMT4C, CMT4G, dHMN5B (DSMA5B), and CMT2A, respectively. The genotype-phenotype correlations were confirmed in all the examined families. We also confirmed that both alleles from the homozygous variants originated from a single ancestor using homozygosity mapping. CONCLUSIONS: This study found five novel mutations as the underlying causes of CMT. Pathogenic mutations in SH3TC2, HK1, and REEP1 have been reported rarely in other populations, suggesting ethnic-specific distribution. This study would be useful for the exact molecular diagnosis and treatment of CMT in Pakistani patients.

Identification of Lead Compounds against Scm (fms10) in Enterococcus faecium Using Computer Aided Drug Designing.

(1) Background: Enterococcus faecium DO is an environmental microbe, which is a mesophilic, facultative, Gram-positive, and multiple habitat microorganism. Enterococcus faecium DO is responsible for many diseases in human. The fight against infectious diseases is confronted by the development of multiple drug resistance in E. faecium. The focus of this research work is to identify a novel compound against this pathogen by using bioinformatics tools and technology. (2) Methods: We screened the proteome (accession No. PRJNA55353) information from the genome database of the National Centre for Biotechnology Information (NCBI) and suggested a potential drug target. I-TASSER was used to predict the three-dimensional structure of the protein, and the structure was optimized and minimized by different tools. PubChem and ChEBI were used to retrieve the inhibitors. Pharmacophore modeling and virtual screening were performed to identify novel compounds. Binding interactions of compounds with target protein were checked using LigPlot. pkCSM, SwissADME, and ProTox-II were used for adsorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. (3) Results: Novel selected compounds have improved absorption and have better ADMET properties. Based on our results, the chemically identified inhibitor ZINC48942 targeted the receptor that can inhibit the activity of infection in E. faecium. This research work will be beneficial for the scientific community and could aid in the design of a new drug against E. faecium infections. (4) Conclusions: It was observed that novel compounds are potential inhibitors with more efficacy and fewer side effects. This research work will help researchers in testing and identification of these chemicals useful against E. faecium.

Effects of core muscle stability on low back pain and quality of life in post- menopausal women: A comparative study.

OBJECTIVE: To determine the effects of core stability exercises on backache and quality of life of postmenopausal women. METHODS: he comparative study was conducted at the Department of Physical Therapy, Margalla General Hospital, Rawalpindi, Pakistan, from February to June 2018, and comprised post-menopausal woman aged 40-60 years having backache who were randomly divided into experimental group A and control group B. Group A underwent core stability exercises along with traditional therapy, while group B had traditional low backache physical therapy. Each participant was treated three days a week for 12 weeks. The outcome was assessed using the manual muscle testing numerical pain rating scale, Oswestry disability index and Utian quality of life scale at baseline, week 6 and week 12. Data was analysed using SPSS 21. RESULTS: Of the 35 subjects initially enrolled, 24(68.5%) completed the study. Of them, 14(58.3%) cases were in group A and 10(41.6%) controls in group B. The overall mean age was 54.54±5.13 years, mean menopause duration was 99.79±50.02 months, and mean duration of backache complaint was 23.95±14.85 months. Differences in outcome were significant between the groups for flexion and extension manual muscle testing and Utian quality of life scale (p<0.05) and non-significant for numerical pain rating scaleand Oswestry disability index (p>0.05). CONCLUSIONS: Core stability exercises were found to have the ability to reduce pain, disability and to improve strength and quality of life.

Homozygous mutations in Pakistani consanguineous families with prelingual nonsyndromic hearing loss.

Autosomal recessive nonsyndromic hearing loss (DFNB) is relatively frequent in Pakistan, which is thought to be mainly due to relatively frequent consanguinity. DFNB genes vary widely in their kinds and functions making molecular diagnosis difficult. This study determined the genetic causes in five Pakistani DFNB families with prelingual onset. The familial genetic analysis identified four pathogenic or likely pathogenic homozygous mutations by whole exome sequencing: two splicing donor site mutations of c.787+1G>A in ESRRB (DFNB35) and c.637+1G>T in CABP2 (DFNB93) and two missense mutations of c.7814A>G (p.Asn2605Ser) in CDH23 (DFNB12) and c.242G>A (p.Arg81His) in TMIE (DFNB6). The ESRRB and TMIE mutations were novel, and the TMIE mutation was observed in two families. The two missense mutations were located at well conserved sites and in silico analysis predicted their pathogenicity. This study identified four homozygous mutations as the underlying cause of DFNB including two novel mutations. This study will be helpful for the exact molecular diagnosis and treatment of deafness patients.

BMT: Bioinformatics mini toolbox for comprehensive DNA and protein analysis.

Background Bioinformatics tools are of great significance and are used in different spheres of life sciences. There are wide variety of tools available to perform primary analysis of DNA and protein but most of them are available on different platforms and many remain undetected. Accessing these tools separately to perform individual task is uneconomical and inefficient. Objective Our aim is to bring different bioinformatics models on a single platform to ameliorate scientific research. Hence, our objective is to make a tool for comprehensive DNA and protein analysis. Methods To develop a reliable, straight-forward and standalone desktop application we used state of the art python packages and libraries. Bioinformatics Mini Toolbox (BMT) is combination of seven tools including FastqTrimmer, Gene Prediction, DNA Analysis, Translation, Protein analysis and Pairwise and Multiple alignment. Results FastqTrimmer assists in quality assurance of NGS data. Gene prediction predicts the genes by homology from novel genome on the basis of reference sequence. Protein analysis and DNA analysis calculates physiochemical properties of nucleotide and protein sequences, respectively. Translation translates the DNA sequence into six open reading frames. Pairwise alignment performs pairwise global and local alignment of DNA and protein sequences on the basis or multiple matrices. Multiple alignment aligns multiple sequences and generates a phylogenetic tree. Conclusion We developed a tool for comprehensive DNA and protein analysis. The link to download BMT is https://github.com/nasiriqbal012/BMT_SETUP.git.

Genome-wide Analysis of Four Enterobacter cloacae complex type strains: Insights into Virulence and Niche Adaptation.

Enterobacter cloacae complex (Ecc) species are widely distributed opportunistic pathogens mainly associated with humans and plants. In this study, the genomes of clinical isolates including E. hormaechei, E. kobei, and E. ludwigii and non-clinical isolate including E. nimipressuralis were analysed in combination with the genome of E. asburiae by using the reference strain E. cloacae subsp. cloacae ATCC 13047; the Ecc strains were tested on artificial sputum media (ASM), which mimics the host, to evaluate T6SS genes as a case study. All five Ecc strains were sequenced in our lab. Comparative genome analysis of the Ecc strains revealed that genes associated with the survival of Ecc strains, including genes of metal-requiring proteins, defence-associated genes and genes associated with general physiology, were highly conserved in the genomes. However, the genes involved in virulence and drug resistance, specifically those involved in bacterial secretion, host determination and colonization of different strains, were present in different genomic regions. For example, T6SS accessory and core components, T4SS, and multidrug resistance genes/efflux system genes seemed vital for the survival of Ecc strains in various environmental niches, such as humans and plants. Moreover, the ASM host-mimicking growth medium revealed significantly high expression of T6SS genes, including PrpC, which is a regulatory gene of the T6SS, in all tested Ecc strains compared to the control medium. The variations in T6SS gene expression in ASM vs. control showed that the ASM system represents a simple, reproducible and economical alternative to animal models for studies such as those aimed at understanding the divergence of Ecc populations. In summary, genome sequencing of clinical and environmental Ecc genomes will assist in understanding the epidemiology of Ecc strains, including the isolation, virulence characteristics, prevention and treatment of infectious disease caused by these broad-host-range niche-associated species.

Analysis of the conformational changes caused by the mutations in mitofusin2 gene by Insilico approach.

OBJECTIVE: To find the effect of pathogenic Mitofusin 2 mutations, responsible for Charcot-Marie-Tooth hereditary neuropathy type 2A, on protein structure. METHODS: The study was conducted at department of biosciences COMSATS University Islamabad, Sahiwal campus from September 2016 to July 2017, and comprised patients with Charcot Marie-Tooth hereditary neuropathy type 2A who were divided into early-onset severe group A and late-onset mild group B. Bioinformatics and molecular analysis was done to find the changes in the protein structure caused by the mutation. Three mutations were selected in two domains of the gene. These were: p. Arg94Trp, p. His165Arg and p. Thr362Met. RESULTS: Of the 10 patients, 5(50%) were in each of the two groups. Change in the structure was predicted in the mutated protein at position p. Arg94Trp, and, due to the mutation, an extra alpha helix was formed in the mutated protein. CONCLUSIONS: Change in the structure of protein can be in a critical position that is involved in the mitochondrial fusion process. However, further studies are required to validate and explain the findings.

In-silico and Molecular Analysis of Reticulon 4asNovel therapeutic option for axonal regeneration.

OBJECTIVES: To find interactions of the ligand with axonali nhibitors, and to check the optimum interactions of existing drugs as inhibitors for the protein that hinders the growth of injured neurons. METHODS: The study was conducted at Kongju National University, Korea from May 2016 to March 2017. It consisted of two parts. Molecular analysis and bioinformatics analysis. The study comprised a family of six with Charcot-Marie-Tooth phenotypes, recommended by a neurologist for molecular analysis on the clinical symptoms to find the mutations responsible for the disease. Blood samples were collected from each family member and total deoxyribonucleic acid was extracted and it was analysed for Reticulon 4 gene by sequencing the coding and intronic regions. However, a missense mutation was found on exon 2 of the gene in the proband and the whole family was subsequently analysed. Bioinformatics analysis and docking studies were carried out to investigate the potential behaviour of Reticulon 4 as therapeutic agent. Sequencing analysis was performed to find the pathoegenic variant responsible for Charcot-Marie-Tooth type 1. RESULTS: After checking pathogenicity of the mutation, Reticulon 4 gene was found to be not involved in Charcot- Marie-Tooth disease type 1. CONCLUSIONS: Reticulon 4 gene was not found to be involved in causing Charcot-Marie-Tooth disease type 1.

Compound heterozygous mutations of SH3TC2 in Charcot-Marie-Tooth disease type 4C patients.

Charcot-Marie-Tooth disease type 4C (CMT4C) is an autosomal recessive neuropathy caused by SH3TC2 mutations, characterized by spine deformities and cranial nerve involvement. This study identified four CMT4C families with compound heterozygous SH3TC2 mutations from 504 Korean demyelinating or intermediate CMT patients. The frequency of the CMT4C was calculated as 0.79% in demyelinating and intermediate patients (n = 504), but it was calculated as 2.02% in patients without PMP22 duplication (n = 198). The CMT4C frequency was similar to patients in Japan, but it was relatively low compared to those patients in other populations. The symptom was less severe and slowly progressed compared to the other AR-CMT. A patient harboring an intermediate neuropathy showed cranial nerve involvement but did not have scoliosis. This study will be helpful in making molecular diagnoses of demyelinating or intermediate CMT due to SH3TC2 mutations.

Effect of torrefaction conditions on the physicochemical characterization of agricultural waste (sugarcane bagasse).

Pakistan is an agricultural country whose agricultural sector employs 43% of the labour force. However, a substantial amount of agricultural waste contributes little economic benefit to the farmers. The annual production of agricultural waste studied in this work, i.e., sugarcane bagasse, is approximately 12 million tonnes per year, and most of that is burned inefficiently. The present work shows that agricultural waste is a significant energy resource that could be used to generate electricity after the application of a simple thermal processing technique (i.e., torrefaction). Torrefaction is a mild pyrolysis treatment in an inert atmosphere that is carried out to improve the physical and chemical properties of biomass. In this study, sugarcane bagasse was torrefied at five different temperatures (200 °C, 225 °C, 250 °C, 275 °C and 300 °C) for four different residence times (15, 30, 45 and 60 min). The physical and chemical properties, such as proximate and ultimate analysis, true density, grindability and hydrophobicity, of the raw and torrefied sugarcane bagasse were investigated. No significant improvement in the characteristics of torrefied waste was found at low torrefaction temperatures (200 °C and 225 °C). However, with the increase in the temperature and residence time torrefaction conditions to 300 °C and 60 min, respectively, a significant improvement was found. The Fourier transform infrared spectroscopy (FTIR) analysis showed that owing to torrefaction, the hydroxyl group content is decreased and carbonyl group content is increased within the fuel. Moreover, a scanning electron microscopy (SEM) study indicated that tiny dispersed particles in the raw sample fused together at a higher torrefaction temperature of 300 °C, forming a tubular structure due to lignin degradation, and the biomass became easy to grind. Thus, torrefaction is an effective approach for improving the characteristics of sugarcane bagasse.

Association of SNP in JPH1 gene with severity of disease in Charcot Marie Tooth 2K patients.

Phenotype varies among the various types of Charcot Marie Tooth Neuropathies(CMT), However the problem arises in cases of same gene but gives a huge variety of phenotype in terms of early and late onset and severity of the disease. To check the impact of rs139723190 SNP on severity of the CMT 2k patients; being a genetic modifier of GDAP1. In the current study CMT 2k patients with early and late onset were analyzed for association of rs139723190 SNP in JPH1 gene responsible for CMT type severe and mild phenotypes. Single nucleotide polymorphisms (SNPs) lead to genetic differences in CMT patients on the basis of severity of the disease. The results of the present study suggest that variants of JPH1 may contribute to the genetic susceptibility as it plays a vital role as genetic modifier in CMT 2K. Candidates risk variants should be further evaluated in studies with a larger sample size.