2026-04-17T01:05:50Zhttps://recercat.cat/oai/request

oai:recercat.cat:10256/281862026-01-30T19:38:16Zcom_2072_452955com_2072_2054col_2072_452960

Unexpected complexity in the molecular diagnosis of spastic paraplegia 11 Mademont Soler, Irene Esteba Castillo, Susanna Jiménez-Xifra, Aida Alemany, Berta Ribas Vidal, Núria Cutillas, Maria Coll Vidal, Mònica Pinsach Abuin, Mel·lina Pagans i Lista, Sara Alcalde Masegu, Mireia Viñas Jornet, Marina Montero-Vale, Mercedes Castro-Miró, Marta de Rodríguez, Jairo Armengol, Lluís Queralt, Xavier Obón, María Paraplegia -- Diagnòstic Paraplegia -- Diagnosis Malalties congènites Genetic disorders Background: Spastic paraplegia 11 (SPG11) is the most prevalent form of autosomal recessive hereditary spastic paraplegia, resulting from biallelic pathogenic variants in the SPG11 gene (MIM *610844). Methods: The proband is a 36-year-old female referred for genetic evaluation due to cognitive dysfunction, gait impairment, and corpus callosum atrophy (brain MRI was normal at 25-years-old). Diagnostic approaches included CGH array, next-generation sequencing, and whole transcriptome sequencing. Results: CGH array revealed a 180 kb deletion located upstream of SPG11. Sequencing of SPG11 uncovered two rare single nucleotide variants: the novel variant c.3143C>T in exon 17 (in cis with the deletion), and the previously reported pathogenic variant c.6409C>T in exon 34 (in trans). Whole transcriptome sequencing revealed that the variant c.3143C>T caused exon 17 skipping. Conclusion: We report a novel sequence variant in the SPG11 gene resulting in exon 17 skipping, which, along with a nonsense variant, causes Spastic Paraplegia 11 in our proband. In addition, a deletion upstream of SPG11 was identified in the patient, whose implication in the phenotype remains uncertain. Nonetheless, the deletion apparently affects cis-regulatory elements of the gene, suggesting a potential new pathogenic mechanism underlying the disease in a subset of undiagnosed patients. Our findings further support the hypothesis that the origin of thin corpus callosum in patients with SPG11 is of progressive nature 2024-06 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion peer-reviewed http://hdl.handle.net/10256/28186 38938072 PMC11211614 http://hdl.handle.net/10256/28186 eng info:eu-repo/semantics/altIdentifier/doi/10.1002/mgg3.2475 info:eu-repo/semantics/altIdentifier/eissn/2324-9269 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess application/pdf Wiley Molecular Genetics and Genomic Medicine, 2024, vol. 12, núm. 6, p. e2475 Articles publicats (D-CM)