MECP2 Mutation Type and Disease Severity in Rett Syndrome
MECP2 Mutation Type and Disease Severity in Rett Syndrome
We recruited 1052 participants who were genotyped and examined over 4940 separate visits. About one-fourth of these individuals were previously analysed and presented in a prior publication. Participants were examined at either the University of Alabama at Birmingham, Baylor College of Medicine, Greenwood Genetic Center, or Boston Children's Hospital or at travel site visits attended by the same clinicians. A clinical severity score (CSS) was calculated at each visit using the following 13 criteria: age of onset of regression, somatic growth, head growth, independent sitting, ambulation (independent or assisted), hand use, scoliosis, language, non-verbal communication, respiratory dysfunction, autonomic symptoms, onset of stereotypies and seizures, as previously described. Of the 1052 participants, 963 met the clinical criteria for either typical or atypical RTT.
Data were tabulated in Microsoft Excel, analysed in SAS and graphed in Origin 8.5.0. Clustered Poisson regression was used to estimate the association between the CSS, or the individual components of the CSS, and types of MECP2 mutations. A Poisson model was deemed appropriate given the ordinal nature of the CSS; the clustered nature of the model was necessary to account for the inclusion of multiple measurements per participant. Using this model, the CSS and its individual components could be compared between subclasses both overall and within age groups. Additionally, for each subclass, the association between the CSS versus age, and separately, time was estimated. As in previous reports, corrections for multiple comparisons were not made when comparing the CSS. A Tukey–Kramer multiple comparisons correction was applied when comparing the individual components of the CSS. For all tests, significant differences with a p<0.05 are reported. Data are presented as average±SD.
Methods
Study Participants
We recruited 1052 participants who were genotyped and examined over 4940 separate visits. About one-fourth of these individuals were previously analysed and presented in a prior publication. Participants were examined at either the University of Alabama at Birmingham, Baylor College of Medicine, Greenwood Genetic Center, or Boston Children's Hospital or at travel site visits attended by the same clinicians. A clinical severity score (CSS) was calculated at each visit using the following 13 criteria: age of onset of regression, somatic growth, head growth, independent sitting, ambulation (independent or assisted), hand use, scoliosis, language, non-verbal communication, respiratory dysfunction, autonomic symptoms, onset of stereotypies and seizures, as previously described. Of the 1052 participants, 963 met the clinical criteria for either typical or atypical RTT.
Data Management and Statistics
Data were tabulated in Microsoft Excel, analysed in SAS and graphed in Origin 8.5.0. Clustered Poisson regression was used to estimate the association between the CSS, or the individual components of the CSS, and types of MECP2 mutations. A Poisson model was deemed appropriate given the ordinal nature of the CSS; the clustered nature of the model was necessary to account for the inclusion of multiple measurements per participant. Using this model, the CSS and its individual components could be compared between subclasses both overall and within age groups. Additionally, for each subclass, the association between the CSS versus age, and separately, time was estimated. As in previous reports, corrections for multiple comparisons were not made when comparing the CSS. A Tukey–Kramer multiple comparisons correction was applied when comparing the individual components of the CSS. For all tests, significant differences with a p<0.05 are reported. Data are presented as average±SD.
