Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary spastic paraplegia

Movement Disorders : Official Journal of the Movement Disorder Society
Dahlia KanchevaAlbena Jordanova

Abstract

Mutations in TUBB4A have been associated with a spectrum of neurological conditions, ranging from the severe hypomyelination with atrophy of the basal ganglia and cerebellum syndrome to the clinically milder dystonia type 4. The presence of movement abnormalities was considered the common hallmark of these disorders. Clinical, neurological, and neuroimaging examinations, followed by whole exome sequencing and mutation analysis, were performed in a highly consanguineous pedigree with five affected children. We identified a novel c.568C>T (p.H190Y) TUBB4A mutation that originated de novo in the asymptomatic mother. The affected subjects presented with an early-onset, slowly progressive spastic paraparesis of the lower limbs, ataxia, and brain hypomyelination, in the absence of dystonia or rigidity. Our study adds complicated hereditary spastic paraplegia to the clinical spectrum of TUBB4A-associated neurological disorders. We establish genotype-phenotype correlations with mutations located in the same region in the tertiary structure of the protein.

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Citations

Oct 20, 2015·Movement Disorders : Official Journal of the Movement Disorder Society·Kishore R KumarChristine Klein
Oct 20, 2015·Movement Disorders : Official Journal of the Movement Disorder Society·Teodora ChamovaIvailo Tournev
Mar 19, 2016·Movement Disorders : Official Journal of the Movement Disorder Society·Aloysius DomingoKatja Lohmann
Apr 16, 2016·Movement Disorders : Official Journal of the Movement Disorder Society·Connie MarrasChristine Klein
Jun 9, 2016·The Cerebellum·Paulo Victor Sgobbi de SouzaAcary Souza Bulle Oliveira
Oct 23, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Daliya KanchevaAlbena Jordanova
Aug 20, 2016·Journal of the Neurological Sciences·Francesco NicitaChiara Aiello
Apr 4, 2018·Continuum : Lifelong Learning in Neurology·Peter Hedera
Aug 7, 2018·Human Mutation·Franca VulinovicAleksandar Rakovic
Aug 15, 2019·Developmental Medicine and Child Neurology·Ganaelle RemerandUNKNOWN RMLX/AHDS Study Group
Jun 26, 2015·Current Opinion in Neurology·Laura Silveira-Moriyama, Jean-Pierre Lin
Oct 9, 2020·International Journal of Molecular Sciences·Antonella SferraEnrico Bertini
Nov 16, 2020·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·Daniela Di BellaEttore Salsano
Jan 26, 2021·Frontiers in Neurology·Stephen Tisch, Kishore Raj Kumar
Mar 2, 2021·Current Neurology and Neuroscience Reports·Lydia Saputra, Kishore Raj Kumar
Aug 21, 2021·Brain : a Journal of Neurology·Edgard VerduraAurora Pujol

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