Genes and chromosomal breakpoints in the Langer-Giedion syndrome region onhuman chromosome 8

The tricho-rhino-phalangeal syndrome type II (TRPS II, or Langer-Giedion sy ndrome) is an example of contiguous gene syndromes, as it comprises the cli nical features of two autosomal dominant diseases, TRPS I and a form of mul tiple cartilaginous exostoses caused by mutations in the EXT1 gene. We have constructed a contig of cosmid, lambda-phage, PAC, and YAC clones, which c overs the entire TRPS I critical region. Using these clones we identified a novel submicroscopic deletion in a TRPS I patient and refined the proximal border of the minimal TRPS1 gene region by precisely mapping the inversion breakpoint of another patient. As a first step towards a complete inventor y of genes in the Langer-Giedion syndrome chromosome region (LGCR) with the ultimate aim to identify the TRPS1 gene, we analyzed 23 human expressed se quence tags (ESTs) and four genes (EIF3S3, RAD21, OPG, CXIV) which had been assigned to human 8q24.1. Our analyses indicate that the LGCR is gene-poor , because none of the ESTs and genes map to the minimal TRPS1 gene region a nd only two of these genes, RAD21 and EIF3S3, are located within the shorte st region of deletion overlap of TRPS II patients. Two genes, OPG and CXIV, which are deleted only in some patients with TRPS II may contribute to the clinical variability of this syndrome.