Article

AIM: To assess the relationship between genotype and neurological progression in
ataxia-telangiectasia (A-T). METHODS: 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. RESULTS: 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). INTERPRETATION:
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.
CI - (c) 2016 Mac Keith Press.

Langue : ANGLAIS