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Gaucher disease (GD) is a lysosomal storage disorder caused by glucocerebrosidase (GBA) deficiency. There are three subcategories of GD: Type 1 is characterized by the absence of primary central nervous system involvement; type 2 is an acute neuropathic disorder; and type 3 is chronic neuropathic. The correlation between genotype and phenotype is sometimes difficult to establish. The F213I (c.754T> A p.Phe252Ile) mutation was reported to be a unique mutation in Asia. To our knowledge, this is the first time the c.754T> A p.(Phe252Ile) mutation (homozygous state) is reported in a Moroccan population and is associated with GD type 2 (two patients) and GD type 3 (one patient). [ABSTRACT FROM AUTHOR]

Background. Hereditary myopathies and muscular dystrophies encompass a diverse group of disorders sharing common clinical features, including muscle weakness, motor developmental delays, and respiratory and bulbar dysfunction. This study aimed to investigate the genetic basis of myopathy in two Moroccan families presenting with these clinical features. Material and methods. Whole exome sequencing (WES) was employed as the primary method for genetic analysis in the two Moroccan families with myopathy symptoms. Candidate variants were confirmed by Sanger sequencing in all DNA available family members. In addition, computational analysis was utilized to assess the impact of the identified variant on the corresponding protein. Results. In the first family, the identified variant in the GNE gene, a homozygous missense substitution (p.Arg246Trp), was associated with GNE myopathy. In the second family, a hemizygous nonsense variant (p.Arg2905Ter) in the DMD gene was identified in the proband, who exhibited symptoms consistent with Duchenne Muscular Dystrophy (DMD). The molecular analysis confirmed the pathogenicity of the identified variants in both GNE myopathy and DMD. The missense variant (p.Arg246Trp) in the GNE gene was found to affect the stability and amino acid interactions of the GNE protein, thus implicating it in GNE myopathy. Additionally, the nonsense variant (p.Arg2905Ter) in the DMD gene provided genetic confirmation of DMD in the second family. Conclusions. This study represents the first genetically confirmed report of GNE myopathy in Morocco, emphasizing the significance of genetic analysis in diagnosing hereditary muscle disorders. The findings also underscore the importance of considering GNE myopathy as part of the differential diagnosis for patients presenting with slowly progressive distal lower extremity weakness. Overall, these results contribute to our understanding of the genetic basis of hereditary myopathies and muscular dystrophies in the Moroccan population. [ABSTRACT FROM AUTHOR]