Molecular cytogenetic characterization of the chromosomal region 2q37 in patients suffering from brachydactyly E including probes for the putative candidate gene LOBO1. H. Starke¹, A. Rump², J. Seidel³, V. Beensen¹, M. Stumm⁴, J. Wirth⁵, A. Heller¹, U. Claussen¹, T. Liehr¹. 1) Institute of Human Genetics and Anthropology, Jena, Germany; 2) Institute of Molecular Biotechnology e.V., Jena, Germany; 3) Childrens Hospital, Jena, Germany; 4) Institute of Human Genetics, Magdeburg, Germany; 5) Max-Planck-Institute for Molecular Genetics, Berlin-Dahlem, Germany.

   We have identified the 3' portion of a large gene located on 2q37 (around STS marker WI8964), which leads to abnormal bone development in transgenetic mice. Given this murine phenotype, the human gene, which we call LOBO1, might be a candidate for brachydactyly E (Rump et al, 1999, Med. Genetik 11, 116). Brachydactyly E, the shortening of the metacarpals and phalanges of hands and/or feet, combined with mental retardation is suspected to be caused in some cases by small deletions in the subtelomeric region in 2q37, detectable only by molecular cytogenetics (Mc Kusick No. 600430). Here we report on 5 clinically confirmed cases suffering from brachydactyly-mental retardation syndrome. The following YAC clones have been used as probes to look for microdeletions: y780a10, y695g12, y770f05, y210e14, y854c09, y627d09, y963g7 and y764g8; additionally, a 3' derived LOBO1 cosmid probe has been used. In case 1 a micro-deletion in 2q37 could be detected, using the YAC y210e14 as probe. The deletion appeared in connection with a structural chromosome aberration described as 46,XY,add(2)(q37). After microdissection and reverse painting this translocation could be described as .rev ish der(2)t(2;acro)(q37;p11.2). As no deletion could be found with the 3' derived LOBO1 cosmid probe, further efforts will be done to clone the lacking parts of the human LOBO1 gene and complementary FISH studies with this new probes will be done. Moreover, to clarify if the LOBO1 gene is a candidate gene for brachydactyly E, mutation screening within the LOBO1 gene will be performed in case1. Acknowledgments: This work was supported by the Madeleine Buehler-Kinderkrebs-Stiftung and a fellowship to A. Heller and H. Starke by the Herbert Quandt Stiftung der VARTA AG.