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

Cortical malformations

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

To read in may...

- Balanced translocations and abnormal phenotypes : what is the relationship ?

- X-linked mental retardation : update 2007.

- Two phases of synaptic dysfunction in the "Rett" mouse.

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.