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 june...

- World Congress on Rett Syndrome : contribute now !

- Genotype-phenotype correlations in Rett Syndrome.

- Female-limited epilepsy : the gene was found !

Naming mutations

There are three main types of mutations.

Mutations are permanent changes in the DNA. When these changes occur in a DNA sequence coding for a protein, they can induce several consequences. First, they can cause the replacement of an aminoacid by another, these are called missense mutations. Next, they can replace an aminoacid by a "stop" instruction causing the interruption of the protein, these are called non-sense mutations. The third type of mutations are deletions or insertions. Deletions are loss of DNA (from 1 base to several thousand). Insertions are gain of DNA (from 1 base to several thousand). In these two latter cases (deletions and insertions) the result for the coding sequence is called a "frameshift", causing the premature occurence of a "stop" instruction interrupting the synthesis of the protein.

Let's take the following sentence that could be the coding sequence for a protein (this sentence has a meaning) :

SHE ATE THE PIE

A missense mutation will produce the following effect (missense mutations sometime allow to preserve a partial meaning, that is a partial function in the case of a protein). In the example below, the modification affects the 10th letter. It is the replacement of the letter "P" by the letter "T". This mutation will be written P10T (replacement of the P in 10th position by a T). The same rules apply for mutations in genes (aminoacid normally present, its position in the protein, the new aminoacid). T158M = threonine (T) at position 158 is replaced by a methionine (M).

SHE ATE THE TIE

A nonsense mutation will have the following effect. The meaning of the sentence is totally lost. The "stop" signals are coded using "*" or the letter "X". The same way of naming mutations is used. In our example (below), the "stop" appears at position 6 to replace the letter "E", we will write E6X. In the case of human genes, an example could be R268X : arginine (R) at position 268 replaced by a stop (X).

SHE AT*

An insertion will have the following effect. Again, the meaning of the sentence is totally lost.

SHE ACT ETH EPI E