Genetics of mental retardation & cortical malformations

Our team

• About us...
• Composition
• Recent publications

Mental retardation

• Introduction
• Positional cloning
• Our work

Rett syndrome

• Introduction
• Clinical signs
• MeCP2 mutations
• Phenotypes
• Our work / Network

Cortical malformations

• Introduction
• Polymicrogyria
• Heterotopia
• Lissencephaly
• Classification
• Genetic causes
• Our work

Epilepsy

• The project
• Our work
• Call for collaboration

To read in march...

- Neuronal migration mechanisms in development and disease.

- A novel sex determination system in a close relative of the house mouse.

- Nup153 and megator define transcriptionally active regions in the Drosophila genome.

MeCP2 mutations

Mutations in the MECP2 gene are found in more than 95% of girls affected by typical Rett syndrome. All types of mutation are found in this gene :

- missense mutations (replacement of one amino acid by another amino acid inside the MECP2 protein), for example T158M (threonin at position 158 replaced by a methionin).

- nonsense mutations (replacement of one amino acid by a signal of arrest of the synthesis of the MECP2 protein), for example R294X (arrest of protein synthesis after amino acid arginin (R) at position 294).

- deletions or insertions (from 1 nucleotide to several thousand).

>>>> If you are not familiar with mutations, please click here<<<<

In addition to the mutations associated with Rett syndrome, we know that mutations in MECP2 are also causing a large number of other neurological disorders :

- "atypical" forms of Rett syndrome (preserved speech, preserved walk, congenital variant).

- a phenotype ressembling Angelman's syndrome.

- non syndromic mental retardation.

- severe neonatal encephalopathy in males.

- autism spectrum disorders.

In all these cases a mutation in the MECP2 gene causes a neurological disorder. One of this disorders is Rett syndrome, which is probably the most frequent phenotype. A description of the other phenotypes caused by a mutation in MECP2 can be found >HERE<.

It is also known that most mutations in the MECP2 gene spontaneously appear on the paternal X chromosome. This is caused by the huge proliferation rate of the male germ cells (highly dividing cells have a higher risk of carrying a mutation). This characteristic explains why most affected children are girls (because the father transmits his X chromosome only to his daughters and his Y chromosome only to his sons).

Additional informations can be obtained from the parent support groups or more specialized websites whose address are given in the "links" section of our site.