Genetic investigation of an Iraqi family with Emery-Dreifuss muscular dystrophy

Abstract Background Emery-Dreifuss muscular dystrophy (EDMD) is a rare genetic disorder characterized by a distinctive combination of symptoms that affect both the skeletal muscles and the heart. This condition falls under the category of humeroperoneal muscular dystrophy, emphasizing its impact on the muscles of the upper arms and lower legs. Methods A 50-year-old male proband with clinical symptoms suggestive of a hereditary disorder underwent clinical evaluation, electrodiagnostic studies, and imaging. His son exhibited similar symptoms, prompting a genetic investigation. Whole-exome sequencing (WES) was performed to identify the genetic basis, and a candidate variant was confirmed using Sanger sequencing. Results A novel heterozygous missense variant in SYNE2 (NM_182914.3:c.12378C > G [p.Ser4126Arg]), located in exon 63 (hg38 chr14-64,098,818-C-G), was identified and confirmed by Sanger sequencing in the proband and his son, but not in the proband’s wife. The variant is segregated with the clinical phenotype and is consistent with autosomal dominant EDMD type 5. Conclusion Our analysis using WES unveiled a novel variant in the SYNE2 gene (c.12378C > G [p.Ser4126Arg]). Given the rarity of SYNE2 -related EDMD type 5, this finding highlights its potential under-recognition in clinical genetics. Further studies in diverse populations are essential to assess its prevalence and pathogenicity. This discovery underscores the value of genetic analysis for family counseling, prenatal screening, and tailored clinical management when such variants are detected.