Updating the profile of C-terminal MECP2 deletions in Rett syndrome
Por:
Bebbington A, Percy A, Christodoulou J, Ravine D, Ho G, Jacoby P, Anderson A, Pineda M, Ben Zeev B, Bahi-Buisson N, Smeets E and Leonard H
Publicada:
1 abr 2010
Resumen:
Objectives This study aimed to compare the phenotype of Rett syndrome
cases with C-terminal deletions to that of cases with different MECP2
mutations and to examine the phenotypic variation within C-terminal
deletions.
Methods Cases were selected from InterRett, an international database
and from the population-based Australian Rett Syndrome Database. Cases
(n = 832) were included if they had a pathogenic MECP2 mutation in which
the nature of the amino acid change was known. Three severity scale
systems were used, and individual aspects of the phenotype were also
compared.
Results Lower severity was associated with C-terminal deletions (n = 79)
compared to all other MECP2 mutations (e. g. Pineda scale C-terminals
mean 15.0 (95% CI 14.0-16.0) vs 16.2 (15.9-16.5). Cases with C-terminal
deletions were more likely to have a normal head circumference (odds
ratio 3.22, 95% CI 1.53-6.79) and weight (odds ratio 2.97, 95% CI
1.25-5.76). Onset of stereotypies tended to be later (median age 2.5
years vs 2 years, p<0.001 from survival analysis), and age of learning
to walk tended to be earlier (median age 1.6 years vs 2 years, p=0.002
from survival analysis). Those with C-terminal deletions occurring later
in the region had lower average severity scores than those occurring
earlier in the region.
Conclusion In terms of overall severity C-terminal deletion cases would
appear to be in the middle of the range. In terms of individual aspects
of phenotype growth and ability to ambulate appear to be particular
strengths. By pooling data internationally this study has achieved the
case numbers to provide a phenotypic profile of C-terminal deletions in
Rett syndrome.
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