title: Longitudinal analysis of the neurological features of ataxia-telangiectasia.
abstract: To assess the relationship between genotype and neurological progression in ataxia-telangiectasia (A-T).
  
  
  
  Clinical and laboratory data were extracted retrospectively from the records of patients attending the UK National Ataxia-Telangiectasia Clinic. Neurological assessments were performed using the A-T Index (Crawford Score) and the A-T Neurological Examination Scale Toolkit (A-T NEST). Variables influencing phenotype were identified by using an information-theoretic approach starting from a maximal model to generate estimates of coefficients for each variable. Per-individual progression was assessed for patients with three or more clinic attendances.
  
  
  
  The genotype could be determined for 125/135 patients. Crawford and A-T NEST scores were well correlated. For both scoring systems the estimated coefficients were significantly positive for Age x kinase activity but not Age x protein expression. Unlike the per-genotype analysis, the individual progression of neurological scores in the 34 patients that attended on three or more occasions was not smooth and linear (and in some cases improved over time).
  
  
  
  Residual kinase activity confers a milder phenotype but there is no difference between kinase-dead and protein-null genotypes. The non-linear progression of individual patients' neurological scores may reflect biological complexity, day-to-day variability, limitations of the assessment methods or a combination of all three.
authors.affiliation: School of Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
authors.forename: Thomas J
authors.identifier: 0000-0003-1669-6666
authors.initials: TJ
authors.lastname: Jackson
authors.affiliation: Nottingham Children's Hospital, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Chow
authors.affiliation: Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors.forename: Mohnish
authors.initials: M
authors.lastname: Suri
authors.affiliation: School of Cancer Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Byrd
authors.affiliation: School of Cancer Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Taylor
authors.affiliation: School of Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, UK.|Nottingham Children's Hospital, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors.forename: William P
authors.initials: WP
authors.lastname: Whitehouse
mesh_terms: D000367:Age Factors; D001260:Ataxia Telangiectasia / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology*; D002648:Child; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009154:Mutation / Q000235:genetics*; D009460:Neurologic Examination; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D012189:Retrospective Studies; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D006113:United Kingdom
chemical_list: D017346:Protein Serine-Threonine Kinases