Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias
Ikusi/ Ireki
Data
2022-10-06Egilea
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
International Journal of Molecular Sciences 23(19) : (2022) // Article ID 11847
Laburpena
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.
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Bestelakorik adierazi ezean, itemaren baimena horrela deskribatzen da:© 2022 by the authors.Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/).