There are an estimated 50 to 100 genes on the X-chromosome which are involved in MRX. Up till date, 16 of those genes have been identified. We want to discover exactly what role these 16 genes, and the ones yet to be identified, play in the development of MRX.

To this aim, the EURO-MRX has at its disposal DNA and pedigrees of over 350 families in which MRX is present. There are strong clues that the mental handicap in these families are caused by a defect in a gene or genes on the X-chromosome.

Mutation-analysis will be carried out on the DNA of the 350 MRX families. This method will show which genes are most frequently mutated. For 11 of the 16 known genes, this analysis has been carried out already. Also, a 100 candidate-genes have been tested on a part of the collection of families. This has resulted in the following findings:

• Almost all known MRX genes only make a small contribution to the development of MRX
• Many more families will have to be tested in order to discover the unknown genes

The genes which have tested positive in the mutation-analysis, will be further tested on a group of 500 patients. Of these 500 patients, the cause of their mental handicap is not known, but unlike the MRX families, they have no family history. If the tested gene is mutated often in the group of 500 patients, it may be suitable for use as a diagnostic test.

Up till now, mutation-analysis has revealed that two genes are more frequently mutated in the 350 MRX families than in the average population. However, this turned out not to be the case for the group of 500 patients, thus eliminating the genes as diagnostic candidates. Although this a somewhat disappointing result, publication of these findings ensure that no unnecessary diagnostic testing is done for these genes.

The role of all identified genes which play a role in MRX, the function will be determined by carrying out functional studies.