title: Clinical variability in ataxia-telangiectasia.
abstract: Ataxia-telangiectasia (A-T) is an autosomal recessive inherited disease characterized by progressive childhood-onset cerebellar ataxia, oculomotor apraxia, choreoathetosis and telangiectasias of the conjunctivae. Further symptoms may be immunodeficiency and frequent infections, and an increased risk of malignancy. As well as this classic manifestation, several other non-classic forms exist, including milder or incomplete A-T phenotypes caused by homozygous or compound heterozygous mutations in the ATM gene. Recently, ATM mutations have been found in 13 Canadian Mennonites with early-onset, isolated, predominantly cervical dystonia, in a French family with generalized dystonia and in an Indian family with dopa-responsive cervical dystonia. In this article, we will describe a Turkish family with three affected sibs. Their phenotypes range from pure cervical dystonia associated with hand tremor to truncal and more generalized dystonic postures. Exome sequencing has revealed the potentially pathogenic compound heterozygous variants p.V2716A and p.G301VfsX19 in the ATM gene. The variants segregated perfectly with the phenotypes within the family. Both mutations detected in ATM have been shown to be pathogenic, and the α-fetoprotein, a marker of ataxia telangiectasia, was found to be increased. This report supports recent literature showing that ATM mutations are not exclusively associated with A-T but may also cause a more, even intra-familial variable phenotype in particular in association with dystonia.
authors.affiliation: Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, and DZNE, German Center for Neurodegenerative Diseases, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany, ebbalohmann@gmx.net.
authors.forename: Ebba
authors.initials: E
authors.lastname: Lohmann
authors.forename: Stefanie
authors.initials: S
authors.lastname: Krüger
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Hauser
authors.forename: Hasmet
authors.initials: H
authors.lastname: Hanagasi
authors.forename: Gamze
authors.initials: G
authors.lastname: Guven
authors.forename: Nihan
authors.initials: N
authors.lastname: Erginel-Unaltuna
authors.forename: Saskia
authors.initials: S
authors.lastname: Biskup
authors.forename: Thomas
authors.initials: T
authors.lastname: Gasser
mesh_terms: D000328:Adult; D001260:Ataxia Telangiectasia / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D001483:Base Sequence; D059472:Exome / Q000235:genetics; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D014421:Turkey
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins