TY - JOUR
T1 - Recent insights into genotype-phenotype relationships in patients with Rett syndrome using a fine grain scale
AU - Fabio, Rosa Angela
AU - Colombo, Barbara
AU - Russo, Silvia
AU - Cogliati, Francesca
AU - Masciadri, Maura
AU - Foglia, Silvia
AU - Antonietti, Alessandro
AU - Tavian, Daniela
PY - 2014
Y1 - 2014
N2 - Mutations in MECP2 gene cause Rett syndrome (RTT), a neurodevelopmental disorder affecting around 1 in 10,000 female births. The clinical picture of RTT appears quite heterogeneous for each single feature. Mutations in MECP2 gene have been associated with the onset of RTT. The most known gene function consists of transcriptional repression of specific target genes, mainly by the binding of its methyl binding domain (MBD) to methylated CpG nucleotides and recruiting co-repressors and histone deacetylase binding to DNA by its transcription repressor domain (TRD). This study aimed at evaluating a cohort of 114 Rett syndrome (RTT) patients with a detailed scale measuring the different kinds of impairments produced by the syndrome. The sample included relatively large subsets of the most frequent mutations, so that genotype-phenotype correlations could be tested. Results revealed that frequent missense mutations showed a specific profile in different areas of impairment. The R306C mutation, considered as producing mild impairment, was associated to a moderate phenotype in which behavioural characteristics were mainly affected. A notable difference emerged by comparing mutations truncating the protein before and after the nuclear localization signal; such a difference concerned prevalently the motor-functional and autonomy skills of the patients, affecting the management of everyday activities.
AB - Mutations in MECP2 gene cause Rett syndrome (RTT), a neurodevelopmental disorder affecting around 1 in 10,000 female births. The clinical picture of RTT appears quite heterogeneous for each single feature. Mutations in MECP2 gene have been associated with the onset of RTT. The most known gene function consists of transcriptional repression of specific target genes, mainly by the binding of its methyl binding domain (MBD) to methylated CpG nucleotides and recruiting co-repressors and histone deacetylase binding to DNA by its transcription repressor domain (TRD). This study aimed at evaluating a cohort of 114 Rett syndrome (RTT) patients with a detailed scale measuring the different kinds of impairments produced by the syndrome. The sample included relatively large subsets of the most frequent mutations, so that genotype-phenotype correlations could be tested. Results revealed that frequent missense mutations showed a specific profile in different areas of impairment. The R306C mutation, considered as producing mild impairment, was associated to a moderate phenotype in which behavioural characteristics were mainly affected. A notable difference emerged by comparing mutations truncating the protein before and after the nuclear localization signal; such a difference concerned prevalently the motor-functional and autonomy skills of the patients, affecting the management of everyday activities.
KW - Autonomy
KW - Cognitive processes
KW - Emotion
KW - MECP2
KW - Motor behaviour
KW - Rett syndrome
UR - http://www.scopus.com/inward/record.url?scp=84924850801&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924850801&partnerID=8YFLogxK
U2 - 10.1016/j.ridd.2014.07.031
DO - 10.1016/j.ridd.2014.07.031
M3 - Article
C2 - 25124696
AN - SCOPUS:84924850801
VL - 35
SP - 2976
EP - 2986
JO - Research in Developmental Disabilities
JF - Research in Developmental Disabilities
SN - 0891-4222
IS - 11
ER -