The Berlin MR Centre

Coordinator:    Prof. Dr. med. Hans-Hilger Ropers
Institution: Max Planck Institut für Molekulare Genetik, Berlin
Elucidating the genetic and molecular causes of MR, implementation of efficient methods for diagnosis and prevention, and research into the therapy of this common disorder are the long-term aims of the Department of Human Molecular Genetics at the MPIMG. In close collaboration with the Department of Medical Genetics at the Charité and with our Iranian partner, we will scale up the recruitment of patients and families. At the Charité Berlin, about 600 mentally retarded patients per year undergo clinical examination, including karyotyping, fra(X) testing and metabolic screening, without leading to a specific diagnosis in > 50 percent of these. Thus, 300 patients with idiopathic (syndromic or non-syndromic) MR can be expected per year. Assuming that 2/3 of these (or their relatives) are willing to participate in this study, the Berlin group should be able to recruit about 600 patients with idiopathic MR during the first 3 years of this study. During this period, we should also be able to recruit another 100 large consanguineous families with ARMR, about two thirds in Iran and one third in Germany. Using our tiling path BAC array and/or a commercial 244k oligonucleotide platform (Agilent) with a resolution of 100 kb or better, array CGH will be performed in all sporadic patients and in one patient from each ARMR family. Moreover, our hitherto unpublished set of array CGH data, obtained by studying almost 2000 patients with MR and a variety of other disorders as well as unaffected family members and healthy controls (Ullmann et al, unpublished), will be made available to the members of the German MR Network. This will be the starting point for a common database of disease-associated and normal copy number variants, which will serve as reference for the interpretation of array CGH data in a diagnostic context. Homozygosity mapping will be performed in all additional consanguineous ARMR families, using Affymetrix or Illumina SNP arrays, and mutation screening of promising candidate genes or entire linkage intervals will be performed to identify the underlying gene defects, making use of novel protocols for the enrichment of defined genomic regions and ‘next generation’ sequencing platforms that are operational at the MPIMG.

Additional relevant Internet link:
German Mental Retardation Network (MRNET)
INTRANET (Members login)