OBJECTIVE: X chromosome inactivation and the MECP2 genotype do not provide the full explanations for the clinical differences between patients with Rett syndrome (RTT), suggesting the involvement of other factors. One MeCP2 target is the brain-derived neurotrophic factor (BDNF) gene. We investigated, according to the MECP2 genotype, the role of the BDNF functional polymorphism (Val66Met) on the severity of RTT. METHODS: This polymorphism in BDNF was analyzed by PCR and dHPLC in 81 patients with RTT. We studied the association between the MECP2 and BDNF genotypes and the clinical features in each patient. RESULTS: We found that some RTT features can be correlated with MECP2 genotypes. Missense mutations are associated with a more severe epileptic phenotype (early onset and drug resistance) than other mutations. Non-sense and late truncating mutations lead to a less severe phenotype regarding walking. The distribution of the Val66Met polymorphism was not significantly different between the different groups in regard to the severity of all tested symptoms. However, girls with RTT bearing the Val66Val genotype tend to present earlier seizures than girls with RTT bearing the Met66 allele. No girls with RTT with the Met66 allele presented early seizures. CONCLUSIONS: Early onset of seizures is linked to the combined MECP2 and BDNF genotypes. The BDNF Met66 allele may protect against seizures, whereas missense mutations in the MBD of MECP2 are more frequently associated with early seizures.
OBJECTIVE: X chromosome inactivation and the MECP2 genotype do not provide the full explanations for the clinical differences between patients with Rett syndrome (RTT), suggesting the involvement of other factors. One MeCP2 target is the brain-derived neurotrophic factor (BDNF) gene. We investigated, according to the MECP2 genotype, the role of the BDNF functional polymorphism (Val66Met) on the severity of RTT. METHODS: This polymorphism in BDNF was analyzed by PCR and dHPLC in 81 patients with RTT. We studied the association between the MECP2 and BDNF genotypes and the clinical features in each patient. RESULTS: We found that some RTT features can be correlated with MECP2 genotypes. Missense mutations are associated with a more severe epileptic phenotype (early onset and drug resistance) than other mutations. Non-sense and late truncating mutations lead to a less severe phenotype regarding walking. The distribution of the Val66Met polymorphism was not significantly different between the different groups in regard to the severity of all tested symptoms. However, girls with RTT bearing the Val66Val genotype tend to present earlier seizures than girls with RTT bearing the Met66 allele. No girls with RTT with the Met66 allele presented early seizures. CONCLUSIONS: Early onset of seizures is linked to the combined MECP2 and BDNF genotypes. The BDNF Met66 allele may protect against seizures, whereas missense mutations in the MBD of MECP2 are more frequently associated with early seizures.
Authors: B Ben Zeev; A Bebbington; G Ho; H Leonard; N de Klerk; E Gak; M Vecsler; M Vecksler; J Christodoulou Journal: Neurology Date: 2009-04-07 Impact factor: 9.910
Authors: Sandra Louise; Sue Fyfe; Ami Bebbington; Nadia Bahi-Buisson; Alison Anderson; Mercé Pineda; Alan Percy; Bruria Ben Zeev; Xi Ru Wu; Xinhua Bao; Patrick Mac Leod; Judith Armstrong; Helen Leonard Journal: Res Autism Spectr Disord Date: 2009-07
Authors: Rosangela Artuso; Filomena T Papa; Elisa Grillo; Mafalda Mucciolo; Dag H Yasui; Keith W Dunaway; Vittoria Disciglio; Maria A Mencarelli; Marzia Pollazzon; Michele Zappella; Giuseppe Hayek; Francesca Mari; Alessandra Renieri; Janine M Lasalle; Francesca Ariani Journal: J Hum Genet Date: 2011-05-19 Impact factor: 3.172