HOLT-GRAM SYNDROME IS A GENETICALLY HETEROGENEOUS DISEASE WITH ONE LOCUS MAPPING TO HUMAN-CHROMOSOME 12Q

Holt-Gram syndrome (HOS) is an autosomal dominant condition affecting the heart and upper limbs. We have sought to identify the location of this gene using microsatellite DNA markers in a linkage study. Of seve n families analysed, five show linkage between HOS and markers on chro mosome 12q. But the two remaining families, phenotypically indistingui shable from the others, do not show this linkage. Analysis with the co mputer program HOMOG indicates that HOS is a heterogeneous disease. Ou r analysis places one HOS locus in a 21cM interval in the distal regio n of chromosome 12q. The localization of a gene for HOS, reported here , represents an important step towards a better understanding of limb and cardiac development.