PMID- 18434641
OWN - NLM
STAT- MEDLINE
DCOM- 20080701
LR  - 20220317
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Linking)
VI  - 70
IP  - 22 Pt 2
DP  - 2008 May 27
TI  - The p.Val66Met polymorphism in the BDNF gene protects against early seizures in 
      Rett syndrome.
PG  - 2145-51
LID - 10.1212/01.wnl.0000304086.75913.b2 [doi]
AB  - 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.
FAU - Nectoux, J
AU  - Nectoux J
AD  - Laboratoire de Biochimie et Genetique Moleculaire, Hopital Cochin, Paris, France.
FAU - Bahi-Buisson, N
AU  - Bahi-Buisson N
FAU - Guellec, I
AU  - Guellec I
FAU - Coste, J
AU  - Coste J
FAU - De Roux, N
AU  - De Roux N
FAU - Rosas, H
AU  - Rosas H
FAU - Tardieu, M
AU  - Tardieu M
FAU - Chelly, J
AU  - Chelly J
FAU - Bienvenu, T
AU  - Bienvenu T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080423
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - AE28F7PNPL (Methionine)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Child
MH  - Cohort Studies
MH  - Female
MH  - Humans
MH  - Methionine/*genetics
MH  - Methyl-CpG-Binding Protein 2/genetics
MH  - Phenotype
MH  - Polymorphism, Genetic/*genetics
MH  - Rett Syndrome/complications/*genetics
MH  - Seizures/etiology/*genetics
MH  - Valine/*genetics
EDAT- 2008/04/25 09:00
MHDA- 2008/07/02 09:00
CRDT- 2008/04/25 09:00
PHST- 2008/04/25 09:00 [pubmed]
PHST- 2008/07/02 09:00 [medline]
PHST- 2008/04/25 09:00 [entrez]
AID - 01.wnl.0000304086.75913.b2 [pii]
AID - 10.1212/01.wnl.0000304086.75913.b2 [doi]
PST - ppublish
SO  - Neurology. 2008 May 27;70(22 Pt 2):2145-51. doi: 
      10.1212/01.wnl.0000304086.75913.b2. Epub 2008 Apr 23.