Participants involved: Nijmegen (responsible), Berlin, Paris, Leuven, Tours.
Collaborating institutes: Lyon, Nicosia, Poznan.

Objectives

1. development of a database, containing clinical and molecular findings of all available MRX families
2. development of a repository of cell lines from one affected individual of each of the above families
3. release of an Internet-accessible MRX database and definition of protols for using the patient material by other researchers

Methodology and study materials

Patients and their families will be investigated by a clinical genetist. Tests include systematic description of dysmorphisms; psychometric testing, including cognitive testing, IQ test, adaptive behaviour testing (all partners involved in this work package).

Diagnostic work-up will be done in at least one of the affected patients, including routine chromosome analysis and fragile X CGG repeat analysis will be performed (all partners involved in this work package).

Mapping of the genetic defect will be performed with a standard set of 30 highly-polymorphic X-chromosomal markers in MRX families giving sufficient statistical power (LOD score > 2).

X-inactivation profiles will be determined in obligate carrier females of MRX families (participant Tours).

The development of the MRX-database will be performed in three steps:

1. design and construction of the database
2. a pilot study, which should result in the finalised database
3. announcement of the release of an internet-accessible MRX database by participant Nijmegen

Construction of a physical database (repository), containing DNA and cell lines of one affected individual of each family (all partners involved in this work package). Material from the repository will be made available to the research community at restricted conditions. Requests for material can be made through the internet-accessible MRX database.