Muscular Dystrophy-Dystroglycanopathy with a Homozygous Pathogenic Variant in the TMEM5 Gene

Alpha-dystroglycanopathies encompass a heterogeneous array of neuromuscular diseases arising from aberrant glycosylation of alpha-dystroglycan. These conditions have been linked to many glycosyltransferases, including TMEM5. A hereditary autosomal recessive (AR) condition has been linked to the TMEM5 gene. Three siblings who have high blood creatine kinase levels and congenital muscular dystrophy were described. Next-generation sequencing (NGS) analysis was used for genetic diagnosis. A noteworthy feature of the clinical trajectory was the somewhat heavier instances with concurrent ocular or cerebral abnormalities. A homozygous mutant area of exon 1 in the TMEM5 gene, c.139del (p.Ala47Argfs*42) frameshift variant, was discovered by NGS. This variation (nonsense) may impact the synthesis or function of proteins by degrading RNA (PVS1). Public data banks did not contain the variation (PM2). In the ClinVar database, all groups categorized the variation as pathogenic/likely pathogenic without supporting data (PP5). This work highlights the importance of TMEM5 in disease pathogenesis while broadening the clinical and mutation range of alpha-dystroglycanopathies. Our research sheds light on the molecular causes of dystroglycanopathies linked to TMEM5, provides guidance for future treatment approaches, and emphasizes the significance of thorough genetic testing for clinical care.