{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hammoud M"],"funding":["Sanofi (Spain)"],"pagination":["1515"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11675868"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(12)"],"pubmed_abstract":["(1) Background: Most rare disease patients endure long delays in obtaining a correct diagnosis, the so-called \"diagnostic odyssey\", due to a combination of the rarity of their disorder and the lack of awareness of rare diseases among both primary care professionals and specialists. Next-generation sequencing (NGS) techniques that target genes underlying diverse phenotypic traits or groups of diseases are helping reduce these delays; (2) Methods: We used a combination of biochemical (thin-layer chromatography and high-performance liquid chromatography-tandem mass spectrometry), NGS (resequencing gene panels) and splicing assays to achieve a complete diagnosis of three patients with suspected metachromatic leukodystrophy, a neurologic lysosomal disorder; (3) Results: Affected individuals in each family were homozygotes for harmful variants in the <i>ARSA</i> gene, one of them novel (c.854+1dup, in family 1) and the other already described (c.640G>A, p.(Ala214Thr), in family 2). In addition, both affected individuals in family 2 were carriers of a known pathogenic variant in an additionallysosomal disease gene, <i>GNPTAB</i> (for mucolipidosis III). This additional variant may modify the clinical presentation by increasing lysosomal dysfunction. (4) Conclusions: We demonstrated the deleterious effect of the novel variant c.854+1dup on the splicing of <i>ARSA</i> transcripts. We also confirmed the involvement of variant c.640G>A in metachromatic leukodystrophy. Our results show the power of diagnostic approaches that combine deep phenotyping, NGS, and biochemical and functional techniques."],"journal":["Genes"],"pubmed_title":["Metachromatic Leukodystrophy in Morocco: Identification of Causative Variants by Next-Generation Sequencing (NGS)."],"pmcid":["PMC11675868"],"funding_grant_id":["LYSOSPAIN"],"pubmed_authors":["Rodrigues D","Villarrubia J","Colon C","Aboussair N","Hammoud M","Fdil N","Dominguez-Ruiz M","Assiri I","Del Castillo FJ","Lanza VF"],"additional_accession":[]},"is_claimable":false,"name":"Metachromatic Leukodystrophy in Morocco: Identification of Causative Variants by Next-Generation Sequencing (NGS).","description":"(1) Background: Most rare disease patients endure long delays in obtaining a correct diagnosis, the so-called \"diagnostic odyssey\", due to a combination of the rarity of their disorder and the lack of awareness of rare diseases among both primary care professionals and specialists. Next-generation sequencing (NGS) techniques that target genes underlying diverse phenotypic traits or groups of diseases are helping reduce these delays; (2) Methods: We used a combination of biochemical (thin-layer chromatography and high-performance liquid chromatography-tandem mass spectrometry), NGS (resequencing gene panels) and splicing assays to achieve a complete diagnosis of three patients with suspected metachromatic leukodystrophy, a neurologic lysosomal disorder; (3) Results: Affected individuals in each family were homozygotes for harmful variants in the <i>ARSA</i> gene, one of them novel (c.854+1dup, in family 1) and the other already described (c.640G>A, p.(Ala214Thr), in family 2). In addition, both affected individuals in family 2 were carriers of a known pathogenic variant in an additionallysosomal disease gene, <i>GNPTAB</i> (for mucolipidosis III). This additional variant may modify the clinical presentation by increasing lysosomal dysfunction. (4) Conclusions: We demonstrated the deleterious effect of the novel variant c.854+1dup on the splicing of <i>ARSA</i> transcripts. We also confirmed the involvement of variant c.640G>A in metachromatic leukodystrophy. Our results show the power of diagnostic approaches that combine deep phenotyping, NGS, and biochemical and functional techniques.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Nov","modification":"2026-05-23T03:08:43.489Z","creation":"2026-05-23T03:07:58.027Z"},"accession":"S-EPMC11675868","cross_references":{"pubmed":["39766783"],"doi":["10.3390/genes15121515"]}}