Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias

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...

ver descrição completa

Detalhes bibliográficos
Autores: Martínez Rubio, Dolores, Hinarejos, Isabel, Sancho, Paula, Gorría Redondo, Nerea, Bernadó Fonz, Raquel, Tello, Cristina, Marco Marín, Clara, Martí Carrera, María Itxaso, Martínez González, María Jesús, García Ribes, Ainhoa, Baviera Muñoz, Raquel, Sastre Bataller, Isabel, Martínez Torres, Irene, Duat Rodríguez, Anna, Janeiro, Patrícia, Moreno, Esther, Pías Peleteiro, Leticia, O’Callaghan Gordo, Mar, Ruiz Gómez, Ángeles, Muñoz, Esteban, Martí, Maria Josep, Sánchez Monteagudo, Ana, Fuster, Candela, Andrés Bordería, Amparo, Pons, Roser Maria, Jesús Maestre, Silvia, Mir, Pablo, Lupo, Vincenzo, Pérez Dueñas, Belén, Darling, Alejandra, Aguilera Albesa, Sergio, Espinós, Carmen
Formato: artículo
Fecha de publicación:2022
País:España
Recursos:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/58251
Acesso em linha:http://hdl.handle.net/10810/58251
Access Level:acceso abierto
Palavra-chave:movement disorders
ataxia
cerebellar atrophy
neurodegeneration with brain iron accumulation (NBIA)
gene panel
exome sequencing
Descrição
Resumo: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.

Registos relacionados