دکتر شهریار نفیسی

Charcot-Marie-Tooth disease type 4G (CMT4G) was first reported in Balkan Gypsies as a myelinopathy starting with progressive distal lower limb weakness, followed by upper limb involvement and prominent distal sensory impairment later in the patient’s life. So far, CMT4G has been only reported in European Roma communities with two founder homozygous variants; g.9712G>C and g.11027G>A, located in the 5’-UTR of the HK1 gene. Here, we present the first Iranian CMT4G patient manifesting progressive distal lower limb weakness from 11 years of age and diagnosed with chronic demyelinating sensorimotor polyneuropathy. Whole-exome sequencing for this patient revealed a homozygous c.19C>T (p. Arg7*) variant in the HK1 gene. This report expands the mutational spectrum of the HK1-related CMT disorder and provides supporting evidence for the observation of CMT4G outside the Roma population. Interestingly, the same Arg7* variant is recently observed in another unrelated Pakistani CMT patient, proposing a possible prevalence of this variant in the Middle Eastern populations.

This retrospective cohort study was conducted to evaluate the efficacy and tolerance of rituximab (RTX) for the management of myasthenia gravis (MG).

This retrospective cross-sectional study was conducted on 61 patients with refractory and non-refractory MG who received RTX. The Myasthenia Gravis Activities of Daily Living (MG-ADL) profile was used to assess MG symptoms and their effects on daily activities at the start of RTX and in the last follow-up. The Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS) scale has been used as an outcome measure after treatment with RTX in the 12th month and the last follow-up.

The mean age of the patients was 40.31 ± 13.53 years (range: 15-78 years). Of 61 patients, eight (13.1%) were double seronegative, 29 (47.5%) had anti-acetylcholine receptor (AChR+) antibody, and 24 (39.3%) had anti-muscle-specific tyrosine kinase antibody (MuSK+). According to the mean rank table, the results of this study showed that the drug was more effective in improving the symptoms of MuSK+ patients compared to the other two groups (P = 0.006). The mean MG-ADL was 4.86 ± 1.83 before treatment and 1.51 ± 2.02 in the last follow-up visit. Paired t-test showed a significant association between MG-ADL before and after treatment in the last visit [t(55): 11.30, 95% confidence interval (CI): 2.79-3.99, P = 0.001)].

This retrospective study showed a considerable effect of RTX as induction therapy in patients with MG, especially those with MuSk+ MG.

The 8-item myasthenia gravis activity of daily living (MG-ADL) questionnaire is a valid and reliable instrument for evaluating myasthenia gravis (MG)-associated disability. This study aims to assess its validity and reliability in the Iranian population.

A total number of 58 patients with MG were qualified for the examination. All 58 patients completed the Persian translation of 15-item Myasthenia Gravis Quality of Life (MG-QOL15) and MG-ADL questionnaires initially, and 30 filled out the MG-ADL questionnaire 2 to 4 weeks after the initial visit. Pearson correlation coefficient of questionnaires, internal consistency using Cronbach's alpha (α), and test-retest repeatability of the questionnaire were evaluated.

The Pearson correlation coefficient of Persian versions of MG-QOL and MG-ADL was 0.93 (P < 0.01). The Persian MG-ADL showed satisfactory internal consistency (Cronbach’s α = 0.89) and test-retest reliability (r = 0.99, P < 0.01).

The Persian MG-ADL is a valid and reliable questionnaire for the determination of activities of daily life in Iranian patients with MG.

Myasthenia gravis (MG) affects the neuromuscular transmission, causing fluctuating muscle weakness and fatigue. This study is carried out with the aim to study the electrophysiologic findings of different subtypes of MG referred to our center in Tehran, Iran. All patients with MG presenting to neurology department of Shariati Hospital, Tehran University of Medical Sciences were enrolled. Clinically, patients with MG were categorized as ocular vs. generalized. The acetylcholine receptor (Ach-R) and muscle-specific receptor tyrosine kinase (anti-MuSK) antibodies were performed. Repetitive Nerve Stimulation (RNS) was performed using the standard method, with supramaximal stimulation of muscles at the 3 Hz frequency by surface electrode at rest. Abductor pollicis brevis (APB) (median nerve), anconeus (radial nerve), trapezius (accessory nerve), and nasalis (facial nerve) muscles were studied in all patients. Single fiber electromyography (SFEMG) was performed by standard method. 196 seropositive patients with MG were included in the study. In electrophysiological studies, RNS was performed for 146 patients of Ach-R-Ab positive MG, with positive results in 110 patients. In addition, SFEMG was conducted for 8 patients with negative RNS, which resulted in 7 positive tests.  Among 23 patients with anti-MuSK-positive MG, RNS was performed for 16 patients, with positive results in 11 patients. The 5 remaining patients with negative RNS test were studied by SFEMG, 4 of whom had positive results. APB compound muscle action potential (CMAP) decrementation significantly correlated with Ach-R-Ab positive MG (P < 0.03). This finding can support the hypothesis that the selection of muscles in electrodignostic study would be important. The electrodiagnostic studies are a good and non-invasive diagnostic tool for MG, and a combination of different distal, proximal, and facial muscles can increase the overall sensitivity of the test.

Guillain-Barre Syndrome (GBS) is an autoimmune acute inflammatory demyelinating polyneuropathy usually elicited by an upper respiratory tract infection. Several studies reported GBS associated with Coronavirus Disease 2019 (COVID-19) infection. In this study, we described nine GBS patients following the COVID-19 vaccine.

In this study, nine patients were introduced from six referral centers for neuromuscular disorders in Iran between April 8 and June 20, 2021. Four patients received the Sputnik V, three patients received the Sinopharm, and two cases received the AstraZeneca vaccine. All patients were diagnosed with GBS evidenced by nerve conduction studies and/or cerebrospinal fluid analysis.

The median age of the patients was 54.22 years (ranged 26-87 years), and seven patients were male. The patients were treated with Intravenous Immunoglobulin (IVIg) or Plasma Exchange (PLEX). All patients were discharged with some improvements.

The link between the COVID-19 vaccine and GBS is not well understood. Given the prevalence of GBS over the population, this association may be coincidental; therefore, more studies are needed to investigate a causal relationship.

Caregivers of patients with amyotrophic lateral sclerosis (ALS) may suffer from anxiety, depression, and reduced quality of life (QoL). Our goal was to evaluate the QoL and mood disorders in caregivers and their correlation with the patients' demographic, physical, and mental conditions.

We analyzed data from 39 patients with ALS and their caregivers. Patients completed questionnaires of anxiety assessed by Generalised Anxiety Disorder Assessment (GAD-7), depression using the Beck Depression Inventory-II (BDI-II), and QoL via 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40). Physical impairment was also measured in the patients using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). Caregivers were also assessed by BDI-II, GAD-7, and 36-item Short-Form Health Survey questionnaire (SF-36).

The prevalence of depression and anxiety in the patients was 82.1% and 71.8%, respectively. Caregivers also had higher rates of anxiety and depression and lower levels of QoL in comparison with the general population (anxiety: 66.7%, depression:  43.6%). Depression and anxiety were considerably associated with worsened QoL in the caregivers. None of the demographic, physical, or mental characteristics of patients with ALS were related to either mood status or QoL of the caregiver population.

Caregivers experience higher rates of anxiety and depression and lower QoL in comparison with the general population. The severity of mood disorders is inversely associated with the physical and mental domains of caregivers' QoL. Nonetheless, QoL in the caregivers is not affected by the physical or mental disability of the patients.

Lipid storage myopathies (LSMs) are rare diseases. The phenotype and genotype of lipid metabolism disorders are heterogeneous and divided into two major groups. Constant or progressive proximal and axial muscle weakness associated with or without metabolic crisis, is often seen in patients with LSM such as primary carnitine deficiency (PCD) or multiple acyl-coenzyme a dehydrogenase deficiency disorder (MADD). On the other hand, rhabdomyolysis triggered by fasting, fever, or physical activity usually occurs in patients with disorders affecting intramitochondrial fatty acid transport and β-oxidation, such as carnitine palmitoyltransferase II deficiency (CPT2), mitochondrial trifunctional protein deficiency and very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD).

In this cross-sectional study, we summarized the clinical profiles and muscle histology of 64 Iranian patients diagnosed with LSM by muscle biopsy. These patients were selected from 3000 patients referred for muscle biopsy to Toos and Mofid children’s hospitals during 2010 to 2016. Their affected siblings were also added to the study.

In our study 45.3% of the patients were men and 54.7% were women. Mean age of the patients was 27.05 years (SD: 14.26) and the mean age of onset of symptoms in these patients was 20.94 (SD: 14.25) years. Most patients (70.3%) had proximal weakness and no bulbar involvement. Only 9.3% of the patients had a positive family history.

LSMs are not uncommon in Iran and their phenotype can mimic inflammatory myopathy or limb girdle muscular dystrophy. Overall the demographic and clinical features of LSMs in Iranian patients were similar to prior reports

Few studies have reported the association of Guillain-Barre syndrome (GBS) and coronavirus disease-2019 (COVID-19) infection. In this study, we reported GBS in six patients infected with COVID-19 and reviewed all existing literature about GBS in association with COVID-19.

This study was performed in three referral centers of COVID-19 in Iran, and six patients with the diagnosis of GBS were enrolled. Patients enrolled in the study with acute progressive weakness according to the demyelinating or axonal variant of GBS, according to Uncini's criteria.

Four of our patients had axonal polyneuropathy, two patients had demyelinating polyneuropathy, and one patient required mechanical ventilation. All our patients had a favorable response to treatment. In one patient, the GBS symptoms recurred four months after the first episode.

Limited case reports suggest a possible association between GBS and COVID-19. Such associations may be an incidental concurrence or a real cause-and-effect linkage; however, more patients with epidemiological studies are necessary to support a causal relationship.

Inherited peripheral neuropathies (IPNs) are a group of neuropathies affecting peripheral motor and sensory neurons. Charcot-Marie-Tooth (CMT) disease is the most common disease in this group. With recent advances in next-generation sequencing (NGS) technologies, more than 100 genes have been implicated for different types of CMT and other clinically and genetically inherited neuropathies. There are also a number of genes where neuropathy is a major feature of the disease such as spinocerebellar ataxia (SCA) and hereditary spastic paraplegia (HSP). We aimed to determine the genetic causes underlying IPNs in Iranian families.

We performed whole exome sequencing (WES) for 58 PMP22 deletion-/duplication-negative unrelated Iranian patients with a spectrum of phenotypes and with a preliminary diagnosis of hereditary neuropathies.

Twenty-seven (46.6%) of the cases were genetically diagnosed with pathogenic or likely pathogenic variants. In this study, we identified genetically strong variants within genes not previously linked to any established disease phenotype in five (8.6%) patients.

Our results highlight the advantage of using WES for genetic diagnosis in highly heterogeneous diseases such as IPNs. Moreover, functional analysis is required for novel and uncertain variants.

Neuromuscular disorders affect physical and mental aspects of a patient and in other words alter the patients’ quality of life (QOL). In the present study, we investigated the validity and reliability of the Persian version of Individualized Neuromuscular QOL (INQOL) to provide a better insight into patients’ QOL.

Original version of the INQOL was translated backward and then forward. The resultant Persian version and a standard questionnaire, 36-Item Short Form Health Survey (SF-36), were then given to 83 participants with neuromuscular disorders. Internal consistency, known-group validity, concurrent validity, and test-retest reliability were assessed.

The scores of matched sections for QOL in the two questionnaires were favorably correlated (P < 0.05). Correlation between test and retest scores was also significant (P < 0.05). Moreover, the Cronbach’s alpha of 0.82 was representative of robust internal consistency between INQOL covering sections.

The Persian version of the INQOL can be used in clinical and research practice to detect changes in QOL which are related to neuromuscular disorders, due to its favorably reliable and valid characteristics.

Motor unit number index (MUNIX) is an electrophysiological technique to give an estimate of functioning motor neurons in a muscle. For any given neurophysiological technique for the use in clinical or research studies, reproducibility between different operators and in a single operator in different times is one of the most important qualities, which must be evaluated and approved by different examiners and centers. After its introduction, testing the reproducibility of MUNIX was the aim of many studies to show this quality of the technique. In this review, we aimed to summarize all the studies, which have been performed up to now to approve MUNIX reproducibility in amyotrophic lateral sclerosis comparing healthy individuals.

Neuropathy means nerve damage, which interferes with the functioning of the peripheral nervous system. It has been mentioned as one of the extra-intestinal manifestations of celiac disease. This study aimed to investigate the prevalence of celiac disease in patients presented with idiopathic neuropathy.
A cross-sectional study was done in patients with idiopathic neuropathy at Shariati Hospital, Tehran. Serological tests including endomysial IgA, tissue transglutaminase (TTG) IgA and IgG, and DGP (deamidated gliadin peptide) IgA, and genetic assessment for HLA DQ2 and DQ8 (human leukocyte antigen) were done for all patients and those who had positive celiac serology and HLA DQ2/DQ8 underwent endoscopy and adequate biopsy samples were taken. Diagnosis was made based on histopathological report of celiac disease.
101 patients with idiopathic neuropathy were enrolled. The mean age was 43.56 ± 10.66 years (range 70-18 years). The prevalence of HLA-DQ2 and HLA-DQ8 positivity in patients with idiopathic neuropathy was 36.6% and 9.9%, respectively. The most common neuropathy subtype in patients with positive HLA-DQ2 and DQ8 was demyelinating PN (Polyneuropathy). One patient (1%) was diagnosed as havine celiac disease.
Although the prevalence of celiac disease in patients with idiopathic neuropathy was similar to the general population, having considered the pravalence of celiac disease, treating this condition with gluten-free diet is of importance.

The calcium channel, voltage-dependent, L-type, alpha 1S subunit (CACNA1S) gene encodes a skeletal Ca2 channel which is involved in calcium-dependent processes such as muscle contraction and neurotransmitter release. Mutations in this gene have been accompanied by hypo- and normokalemic periodic paralysis, thyrotoxic periodic paralysis, and susceptibility to malignant hyperthermia. We report the clinical and genetic findings in a patient diagnosed with metabolic myopathy who had episodic attacks of muscle pain and weakness but with no family background of the disease. Next-generation sequencing (NGS) using a panel targeting metabolic myopathy and myotonia genes identified a de novo heterozygous pathogenic variant c.3724A>G, p.Arg1242Gly, in exon 30 of CACNA1S. As the second report of this variant, this case may broaden the CACNA1S-related disease spectrum to include normokalemic periodic paralysis.

Pompe disease is a rare neuromuscular genetic disorder and is classified into two forms of early and late-onset. Over the past two decades, mitochondrial abnormalities have been recognized as an important contributor to an array of neuromuscular diseases. We therefore aimed to compare mitochondrial copy number and mitochondrial displacement-loop sequence variation in infantile and adult Pompe patients.
In this retrospective study, the mitochondrial D-loop sequence was analyzed by polymerase chain reaction (PCR) and direct sequencing to detect possible variation in 28 Pompe patients (17 infants and 11 adults). Results were compared with 100 healthy controls and sequences of all individuals were compared with the Cambridge reference sequence. Real-time PCR was used to quantify mitochondrial DNA copy number.
Among 59 variants identified, 37(62.71%) were present in the infant group, 14(23.333%) in the adult group and 8(13.333%) in both groups. Mitochondrial copy number in infant patients was lower than adults (P The 317-318 ins CCC was detected as a new mitochondrial variant in Pompe patients.

Neuromuscular disorders (NMDs) include a broad range of diseases affecting muscles, nerves and neuromuscular junctions. Approximately 761 different disorders occur in this group which is subdivided into 16 different subgroups with 406 known genes. NMDs are genetically and clinically heterogeneous conditions. The advent of next generation sequencing (NGS) approaches has accelerated the pace of discovery of NMDs genes. In this study, we describe the validation of an NGS panel, for comprehensive mutation detection in NMDs patients. During a year, a total of 46 patients were examined, mostly offspring of consanguineous marriages. Data analysis was performed to identify the most probable pathogenic rare variants in known NMD genes. Co-segregation analysis and genotype–phenotype correlation led to identification of causal variants. In 33 out of 46 patients (71.7%), the pathogenic variant was identified in the following known genes: CAPN3, Col6A1, Col6A3, DMD, DYSF, FHL1, GJB1, ISPD, LAMA2, LMNA, PLEC1, RYR1, SGCA, SGCB, SYNE1, TNNT1 and 22 novel pathogenic variants were detected which is quite high compared to the overall diagnostic yield of no more than 50% in most other reports.

Charcot-Marie-Tooth disease (CMT) is the most common inherited neurological disorder, affecting both motor and sensory peripheral nerves. Neurophysiological patterns divide CMT into three main groups: demyelinating CMT1 (upper limb motor nerve conduction velocity (MNCV) 38 m/s) and intermediate CMT (MNCV 25-45 m/s). CMT has been also categorized based on the mode of inheritance and subtypes are defined according to the mutant genes. Duplication of 1.5 Mb of chromosome 17, encompassing PMP22 gene, accounts for up to 80% of cases with demyelinating neuropathies in its most prevalent type, CMT1A. Deletion of the same region is responsible for Hereditary Neuropathy with liability to Pressure Palsies (HNPP).
The Clinical and genetic heterogeneity of CMT disease has been always considered as one of the major challenges in diagnostic procedure. Although, most current genetic testing strategies for CMT are mainly based on the family history and data on clinical and neurophysiological assessments, variable degree of phenotypic expression and large number of genes involved in CMT bring challenges to the diagnosis. Hence, in everyday practice in genetic laboratories, the detection rate for this group of patients may significantly influenced by this genetic and clinical heterogeneity. Our aim was to present our experience on the applicability of the recommended strategies for CMT diagnosis.
Dosage analysis using multiplex ligation probe amplification (MLPA), a specific and sensitive quantitative method, is considered as the first step in the detection of demyelinating CMT. MLPA analysis of 30 unrelated individuals who were referred to Kariminejad-Najmabadi Pathology and Genetics Center with general diagnosis of polyneuropathy, revealed 7 cases of CMT1A (due to 1.5 Mb duplication) and a case with HNPP (1.5 Mb deletion).
This detection rate of about 25% for MLPA testing elucidates the need for a better understanding of the circumstances under which the genetic test is requested. Considering the clinical data, when MLPA fails to detect the causative gene, patients are supposed to be subjected to extended analysis. Implementation of NGS in diagnosis of CMT has made a powerful platform to detect the full spectrum of CMT mutations, which provides an efficient and cost effective genetic testing and therefore an increased detection rate.

Decreasing the population and activation of inflammatory T helper cells in multiple sclerosis (MS) patients using vitamin A derivatives (retinoic acids) has been well documented. The present study determined the effect of vitamin A supplementation on psychiatric signs in MS patients. The subjects were 101 relapsing-remitting MS patients enrolled in a placebo-controlled randomized clinical trial. The treatment group was administered 25000 IU/d retinyl palmitate (RP) for 6 months followed by 10000 IU/d RP for another 6 months. The results for baseline characteristics, modified fatigue impact scale and Beck Depression Inventory-II were recorded at the beginning and end of the one-year study. The non-normal distribution data was compared between groups using a nonparametric test and normal distribution data was analyzed using a parametric test. (ClinicalTrials.gov Identifiers: NCT01417273). The results showed significant improvement in the treatment group for fatigue (p=0.004) and depression (p=0.01). Vitamin A supplementation helped during interferon therapy in the treatment process and improved psychiatric outcomes for anti-inflammatory mechanisms.

Despite the genetic heterogeneity reported in familial ALS (FALS), SOD1 gene mutations are the most frequent cause of FALS, accounting for around 20% of familial cases (ALS1) and isolated sporadic cases. Mutant forms of SOD1 exhibit toxicity that promotes the death of motor neurons. It is well documented that FALS produces protein aggregates in the motor neurons of FALS patients, which have been found to be associated to mitochondria.
In this study, we cloned the SOD1 gene, using reverse transcriptase-polymerase chain reaction (RT-PCR) method, from both a healthy control and a living 79 -year-old man with diagnosis of sporadic form of ALS who had shown unusual rapid progression of disease. RNA samples were available from lymphocytes of them. pET28a expression system and BL21 chemically competent Escherichia coli strain as host were used for protein expression.
DNA Sequencing data showed both heterozygosis C to G transition at nucleotide position 21 leading to a C6W changing at protein level and a deletion at nucleotides position 73 to 169 leading to complete deletion of exon two.
Based on this case study, it appears that SOD-1 mutation and its protein aggregation is associated with the progression of ALS.

Non-dystrophic myotonias are a heterogeneous set of skeletal, muscular channelopathies, which have been associated with point mutations within sodium channel α-subunit (SCN4A) gene. Because exons 22 and 24 of SCN4A gene are recognized as hot spots for this disease, the purpose of the study is to identify mutation in exons 22 and 24 of SCN4A gene in Iranian non-dystrophic myotonias patients. In this study, 28 Iranian patients with non-dystrophic myotonia analyzed for the mutation scanning in exons 22 and 24 of SCN4A gene by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and sequencing. We found 29073G>C substitution in SCN4A gene in one case and 31506A>G substitution in seven cases. The 29073G>C substitution causes a missense mutation G1306A, located in the conserved cytoplasmic loop connecting repeat III and IV of the SCN4A channel but, 31506A>G substitution do not alter amino acid in SCN4A protein. G1306A residue is located in functionally important protein region. In “hinged-lid model” for Na+ channel inactivation in which glycines1306 act as the hinge of the lid occluding the channel pore. Mutation in this region slowed fast inactivation. Therefore, it might be a pathogenic mutation. The causal relationship of this mutation with the disease is an object for further discussion.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disorder in European populations. ALS can be sporadic ALS (SALS) or familial ALS (FALS). Among 20 known ALS genes, mutations in C9orf72 and superoxide dismutase 1 (SOD1) are the most common genetic causes of the disease. Whereas C9orf72 mutations are more common in Western populations, the contribution of SOD1 to ALS in Iran is more than C9orf72. At present, a clear genotype/phenotype correlation for ALS has not been identified. We aimed to perform mutation screening of SOD1 in a newly identified Iranian FALS patient and to assess whether a genotype/phenotype correlation for the identified mutation exists. The five exons of SOD1 and flanking intronic sequences of a FALS proband were screened for mutations by direct sequencing. The clinical features of the proband were assessed by a neuromuscular specialist (SN). The phenotypic presentations were compared to previously reported patients with the same mutation. Heterozygous c.260A > G mutation in SOD1 that causes Asn86Ser was identified in the proband. Age at onset was 34 years and site of the first presentation was in the lower extremities. Comparisons of clinical features of different ALS patients with the same mutation evidenced variable presentations. The c.260A > G mutation in SOD1 that causes Asn86Ser appears to cause ALS with variable clinical presentations.

Many studies have shown that active vitamin A derivatives suppress the formation of pathogenic T cells in multiple sclerosis (MS) patients. The aim of the present study is to determine the impact of vitamin A on disease progression in MS patients. A total of 101 relapsing-remitting MS (RRMS) patients were enrolled in a 1-year placebo-controlled randomized clinical trial. The treated group received 25000 IU/d retinyl palmitate for six month followed by 10000 IU/d retinyl palmitate for another six month. Results for the expanded disability status scale (EDSS) and multiple sclerosis functional composite (MSFC) were recorded at the beginning and the end of the study. The relapse rate was recorded during the intervention. Patients underwent baseline and follow up brain MRIs. The results showed "Mean ± SD" of MSFC changes in the treated group was (-0.14 ± 0.20) and in the placebo group was (-0.31 ± 0.19). MSFC was improved in the treatment group significantly (p < 0.001). There was no significant differences between the "Mean ± SD" of EDSS changes in the treated (0.07 ± 0.23) and the placebo (0.08 ± 0.23) groups (p = 0.73). There was also no significant differences between the "Mean ± SD" of annualized relapse rate in the treated group (-0.36 ± 0.56) and placebo (-0.53 ± 0.55) groups (p = 0.20). The "Mean ± SD" of enhanced lesions in the treatment (0.4 ± 1.0) and in the placebo (0.2 ± 0.6) groups were not significantly different (p = 0.26). Volume of T2 hyperintense lesions "Mean ± SD" was not significantly different between treatment (45 ± 137) and placebo (23 ± 112) groups after intervention (p = 0.23). Vitamin A improved total MSFC score in RRMS patients, but it did not change EDSS, relapse rate and brain active lesions.

Mutations in plectin, a widely expressed giant cytolinker protein can lead to different diseases mostly with signs of muscular dystrophy (MD) and skin blistering. The only report of plectin-related disease without skin involvement is limb-girdle muscular dystrophy type 2Q (LGMD2Q) phenotype, showing early-onset limb-girdle muscular dystrophy symptoms with progressive manner and no cranial muscle involvement. Here, we report a non-consanguineous Iranian family with two affected sisters showing progressive limb and ocular muscle weakness. Whole Exome Sequencing (WES) led to identification of a compound heterozygous mutations, p.Gln1022Ter (c.3064C>T) and p.Gly3835Ser (c.11503G>A), in PLEC gene. To the best of our knowledge, this would be the first report of a patient with LGMD and myasthenic symptoms without any skin involvement, caused by plectinopathy. This observation extends the phenotypic spectrum of PLEC related diseases and suggests a variable expression of the PLEC- related symptoms.