The Neurodevelopmental Disorders research group of the Girona Biomedical Research Institute (IDIBGI) and the Health Care Institute (IAS) has published a new study in the journal Molecular Genetics & Genomic Medicine. The study describes the complex genetic diagnosis of a 36-year-old patient with spastic paraparesis type 11 (SPG11), a rare disease that affects mobility and the nervous system.
Spastic paraparesis type 11 is an inherited disorder that causes walking difficulties and cognitive impairments. This disorder is related to biallelic mutations in the SPG11 gene. In this study, the team has identified a new genetic variant that causes "exon skipping" or loss of a key segment of the SPG11 gene. This variant, together with another pathogenic variant in the other allele of the gene, prevents the proper functioning of the spatacsin protein in the patient and causes the clinical manifestations of the disease.
The research team, headed by Dr. María Obón and with Dr. Irene Mademont as first author, has also observed another relevant finding: a deletion in a region close to the gene, which could affect its regulatory regions and, therefore, be involved in the expression of the disease. This combination of genetic variants has allowed us to better understand the patient's case and propose possible new avenues for the diagnosis of other patients with this condition.
The study represents another step in understanding this disorder and reveals the complexity of its genetic diagnosis. Through microarray, massive sequencing and transcriptomics techniques, researchers have been able to detect variants that could not be identified before. This new information opens the door to finding out, in future research, how these variants can affect the development of the disease.
In this article, led by the Neurodevelopmental Disorders research group of the IDIBGI – IAS, headed by Dr. Susanna Esteba Castillo, researchers from the Cardiovascular Genetics and Neurodegeneration and Neuroinflammation research groups of the IDIBGI have also participated, as well as members of the Territorial Clinical Laboratory of Girona.
Article de referència: Mademont-Soler I, Esteba-Castillo S, Jiménez-Xifra A, Alemany B, Ribas-Vidal N, Cutillas M, Coll M, Pinsach ML, Pagans S, Alcalde M, Viñas-Jornet M, Montero-Vale M, de Castro-Miró M, Rodríguez J, Armengol L, Queralt X, Obón M. Unexpected complexity in the molecular diagnosis of spastic paraplegia 11. Mol Genet Genomic Med. 2024 Jun;12(6):e2475. doi: 10.1002/mgg3.2475. PMID: 38938072; PMCID: PMC11211614.
