فهرست نشریات علمی دسترسی آزاد ایران

Variants in the immunoglobulin mu-binding protein 2 (IGHMBP2) gene are associated with two phenotypes: The first phenotype is spinal muscular atrophy with respiratory distress type 1 (SMARD1), an alpha motor neuron disorder characterized by diaphragmatic paralysis and early death, often within the first year of life. The second phenotype is Charcot-Marie-Tooth disease type 2S (CMT2S), a slowly progressive axonal neuropathy marked by sensory loss and typically lacking respiratory involvement. This study aimed to identify the genetic cause of CMT2S in an Iranian family and to review previously reported variants and clinical features of CMT2S in the literature. Exome sequencing was performed on the affected proband. The candidate variant was subsequently validated in additional family members using Sanger sequencing. The pathogenicity and novelty of the variant were assessed using in silico prediction tools and available databases. We identified a novel homozygous variant, c.509T>C (p. Leu170Pro), in the IGHMBP2 gene. 60 patients (59 patients + 1 case) were analyzed with CMT2S in our literature review. The main symptoms observed among these patients included muscle weakness and atrophy, absent reflexes, foot deformities, and gait disturbances. Atypical symptoms, including respiratory problems, gastrointestinal disturbances, and bladder dysfunction, were reported in a minority of cases. Among patients with an available age of onset, the mean age was 3.40 (SD± 3.83 years), with an interquartile range of 4.33 years. Across the analyzed patients, 98 total variants were included in the final mutational spectrum. Among these variants, c.1235+3A>G (p.Ala355Leufs*10) was the most frequently reported variant, occurring in seven patients. We report the second known case of CMT2S in a patient of Iranian descent, associated with a novel biallelic variant in the IGHMBP2 gene. Our findings, along with previous findings from the literature, expand the mutational spectrum of IGHMBP2 in CMT2S, contributing to a better understanding of its clinical and genetic heterogeneity.