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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]

• NGS was used to identify homozygous mutation in two unrelated patients with neuromuscular disorders. • SIL1 mutation identified for the first time in the Moroccan population, associated to MSS. • Novel homozygous frames-shift FA2H mutation, responsible for the SPG-35. The identification of underlying genes of genetic conditions has expanded greatly in the past decades, which has broadened the field of genes responsible for inherited neuromuscular diseases. We aimed to investigate mutations associated with neuromuscular disorders phenotypes in 2 Moroccan families. Next-generation sequencing combined with Sanger sequencing could assist with understanding the hereditary variety and underlying disease mechanisms in these disorders. Two novel homozygous mutations were described in this study. The SIL1 mutation is the first identified in the Moroccan population, the mutation was identified as the main cause of Marinesco-Sjogren syndrome in one patient. While the second mutation identified in the fatty acid 2-hydroxylase gene (FA2H) was associated with the Spastic paraplegia 35 in another patient, both transmitted in an autosomal recessive pattern. These conditions are extremely rare in the North African population and may be underdiagnosed due to overlapping clinical characteristics and heterogeneity of these diseases. We have reported in this study mutations associated with the diseases found in the patients. In addition, we have narrowed the phenotypic spectrum, as well as the diagnostic orientation of patients with neuromuscular disorders, who might have very similar symptoms to other disease groups. [ABSTRACT FROM AUTHOR]

We summarize here a 15-year-old Moroccan girl who was diagnosed with Lafora disease based on histopathological findings of skin biopsy. Diagnosis was confirmed by histopathological analysis of axillary skin biopsy, which revealed typical Lafora bodies in the epithelium of the sweat gland ducts (Fig). Epilepsy Res. 145, 2018, 169-177 3 M.A. Garcia-Gimeno, E. Knecht, P. Sanz, Lafora disease: a ubiquitination-related pathology. [Extracted from the article]