Clinical variability in ataxia–telangiectasia

详细信息    查看全文

• 作者：Ebba Lohmann ; Stefanie Krüger ; Ann-Kathrin Hauser ; Hasmet Hanagasi…
• 关键词：ATM ; Dystonia ; Turkey ; Phenotype
• 刊名：Journal of Neurology
• 出版年：2015
• 出版时间：July 2015
• 年：2015
• 卷：262
• 期：7
• 页码：1724-1727
• 全文大小：339 KB
• 参考文献：1.Gatti R, Ataxia-Telangiectasia (1999) [Updated 2010 Mar 11]. In: Pagon RA, Adam MP, Ardinger HH et al (eds) GeneReviews? [Internet]. Seattle: University of Washington, Seattle; 1993-014. http://?www.?ncbi.?nlm.?nih.?gov/?books/?NBK26468/-/span>
  2.Hiel JA, van Engelen BG, Weemaes CM et al (2006) Distal spinal muscular atrophy as a major feature in adult-onset ataxia telangiectasia. Neurology 67:346-49PubMed View Article
  3.Meneret A, Ahmar-Beaugendre Y, Rieunier G et al (2014) The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia. Neurology 83:1087-095PubMed View Article
  4.Yanofsky RA, Seshia SS, Dawson AJ et al (2009) Ataxia-telangiectasia atypical presentation and toxicity of cancer treatment. Can J Neurol Sci 36:462-67PubMed View Article
  5.Meissner WG, Fernet M, Couturier J et al (2013) Isolated generalized dystonia in biallelic missense mutations of the ATM gene. Mov Disord 28:524-28View Article
  6.Cummins G, Jawad T, Taylor M, Lynch T (2013) Myoclonic head jerks and extensor axial dystonia in the variant form of ataxia telangiectasia. Parkinsonism Relat Disord 19(12):1173-174PubMed View Article
  7.Saunders-Pullman R, Raymond D, Stoessl AJ et al (2012) Variant ataxia-telangiectasia presenting as primary appearing dystonia in Canadian-Mennonites. Neurology 78:649-57PubMed Central PubMed View Article
  8.Charlesworth G, Mohire MD, Schneider SA, Stamelou M, Wood NW (2013) Bhatia KP Ataxia telangiectasia presenting as dopa-responsive cervical dystonia. Neurology 81:1148-151PubMed Central PubMed View Article
  9.Carillo F, Schneider SA, Taylor AM, Srinivasan V, Kapoor R (2009) Bathia KP Prominent oromandibular dystonia and pharyngeal telangiectasia in atypical ataxia telangiectasia. Cerebellum 8:22-7View Article
  10.Scott SP, Bendix R, Chen P, Clark R, Dork T, Lavin MF (2002) Missense mutations but not allelic variants alter the function of ATM by dominant interference in patients with breast cancer. Proc Natl Acad Sci U S A 99:925-30PubMed Central PubMed View Article
  11.Shaikh AG, Zee DS, Mandir AS, Lederman HM, Crawford TO (2013) Disorders of upper limb movements in ataxia-telangiectasia. PLoS ONE 8:e67042PubMed Central PubMed View Article
  12.Micol R, Ben Slama L, Suarez F et al (2011) Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype. J Allergy Clin Immunol 128:382-89PubMed View Article
  13.Verhagen MM, Last JI, Hogervorst FB et al (2012) Presence of ATM protein and residual kinase activity correlates with the phenotype in ataxia-telangiectasia: a genotype-phenotype study. Hum Mutat 33:561-71PubMed View Article
  
• 作者单位：Ebba Lohmann (1) (2)
  Stefanie Krüger (3)
  Ann-Kathrin Hauser (1)
  Hasmet Hanagasi (2)
  Gamze Guven (4)
  Nihan Erginel-Unaltuna (4)
  Saskia Biskup (3)
  Thomas Gasser (1)
  
  1. 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
  2. Behavioural Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
  3. CeGaT, GmbH, Tübingen, Germany
  4. Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Neurology
  Neurosciences
  Neuroradiology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1459

文摘

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.