RT Journal Article
T1 Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias.
A1 Martínez-Rubio, Dolores
A1 Hinarejos, Isabel
A1 Sancho, Paula
A1 Gorría-Redondo, Nerea
A1 Bernadó-Fonz, Raquel
A1 Tello, Cristina
A1 Marco-Marín, Clara
A1 Martí-Carrera, Itxaso
A1 Martínez-González, María Jesús
A1 García-Ribes, Ainhoa
A1 Baviera-Muñoz, Raquel
A1 Sastre-Bataller, Isabel
A1 Martínez-Torres, Irene
A1 Duat-Rodríguez, Anna
A1 Janeiro, Patrícia
A1 Moreno, Esther
A1 Pías-Peleteiro, Leticia
A1 Gordo, Mar O'Callaghan
A1 Ruiz-Gómez, Ángeles
A1 Muñoz, Esteban
A1 Martí, Maria Josep
A1 Sánchez-Monteagudo, Ana
A1 Fuster, Candela
A1 Andrés-Bordería, Amparo
A1 Pons, Roser Maria
A1 Jesús-Maestre, Silvia
A1 Mir, Pablo
A1 Lupo, Vincenzo
A1 Pérez-Dueñas, Belén
A1 Darling, Alejandra
A1 Aguilera-Albesa, Sergio
A1 Espinós, Carmen
K1 ataxia
K1 cerebellar atrophy
K1 exome sequencing
K1 gene panel
K1 movement disorders
K1 neurodegeneration with brain iron accumulation (NBIA)
AB 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.
YR 2022
FD 2022-10-06
LK http://hdl.handle.net/10668/21202
UL http://hdl.handle.net/10668/21202
LA en
DS RISalud
RD Apr 8, 2025