Artículo
Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias
Autor/es | Martínez Rubio, Dolores
Hinarejos, Isabel Sancho, Paula Gorría Redondo, Nerea Bernadó Fonz, Raquel Tello, Cristina Mir Rivera, Pablo Espinós, Carmen |
Departamento | Universidad de Sevilla. Departamento de Medicina |
Fecha de publicación | 2022-12-08 |
Fecha de depósito | 2023-06-07 |
Publicado en |
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Resumen | Our clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are ... Our clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits are known. The patients were evaluated using standardised clinical assessments of ataxia and MDs. First, NBIA genes were analysed by Sanger sequencing and 59 patients achieved a diagnosis, including the detection of the founder mutation PANK2 p.T528M in Romani people. Then, we used a custom panel MovDisord and/or exome sequencing; 29 cases were solved with a great genetic heterogeneity (34 different mutations in 23 genes). Three patients presented brain iron deposits with Fe-sensitive MRI sequences and mutations in FBXO7, GLB1, and KIF1A, suggesting an NBIA-like phenotype. Eleven patients showed very early-onset ataxia and CA with cortical hyperintensities caused by mutations in ITPR1, KIF1A, SPTBN2, PLA2G6, PMPCA, and PRDX3. The novel variants were investigated by structural modelling, luciferase analysis, transcript/minigenes studies, or immunofluorescence assays. Our findings expand the phenotypes and the genetics of MDs and ataxias with early-onset CA and cortical hyperintensities and highlight that the abnormal brain iron accumulation or early cerebellar gliosis may resembling an NBIA phenotype. |
Agencias financiadoras | Instituto de Salud Carlos III European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) Fundació La Marató TV3 Generalitat Valenciana Ministerio de Educación, Cultura y Deporte (MECD). España Fundación Española Per Amor a l’Art |
Identificador del proyecto | PI18 /00147
PI21/00103 20143130 20143131 PROMETEO/2018/135 FPU15/00964 FI19/00072 |
Cita | Martínez Rubio, D., Hinarejos, I., Sancho, P., Gorría Redondo, N., Bernadó Fonz, R., Tello, C.,...,Espinós, C. (2022). Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias. International Journal of Molecular Sciences, 23 (19), 11847. https://doi.org/10.3390/ijms231911847. |
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