PubMed · 311768
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
A Ruprecht, A S Ross. 1978. Multiple mandibular buccal exostoses.. https://pubmed.ncbi.nlm.nih.gov/311768/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
OBJECTIVE: To identify the gene causing hereditary multiple exostoses in a Chinese pedigree. METHODS: Linkage analysis was carried out in the family using microsatellite markers on chromosome 8, 11 and 19 respectively. To detect the mutation, the whole coding sequence and the intron-exon boundaries of the candidate gene were amplified and sequenced. The reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to amplify the mutated mRNA. RESULTS: The disease-causing gene of the family was linked to the EXT2 locus on chromosome 11. A mutation IVS2+1G>A was detected in EXT2 and resulting in 221 bp deletion from 316 to 536 of coding sequence(CDS), which was co-segregated with the disease phenotype. This change led to deletion from codon 106 to codon 178 and subsequent 2 nucleotides, producing a frameshift and truncated protein of 125 aa. CONCLUSION: The mutation IVS2+1G>A is the disease-causing mutation in the Chinese pedigree with hereditary multiple exostoses.
EXT1 and EXT2 are genes that have been shown to cause hereditary multiple exostosis (HME), a syndrome marked by the formation of bony growths juxtaposed to the growth plate. These genes are members of a growing family of proteins with glycosyltransferase activity required for the synthesis of heparan sulfate chains. This protein activity is predicted to play a role in the expression of proteoglycans on the cell surface and in the extracellular matrix. We and others have previously suggested that a two-hit mutational model applies to the development of an exostosis where a germline mutation coupled with a somatic mutation results in the loss of EXT1 or EXT2 function and subsequent tumor formation. We report the direct sequencing and loss of heterozygosity (LOH) analysis of 12 exostoses from 10 HME families, 4 solitary exostoses, and their corresponding constitutional DNA. Of the 16 exostoses screened, we find only one solitary case in which two somatic mutations, a deletion and an LOH, are present. This provides limited support for the two-hit hypothesis involving the EXT1 and EXT2 genes for the development of an exostosis. Alternative models are developed based on the functional significance of EXT proteins in heparan sulfate biosynthesis.
Cartilage-hair hypoplasia is a chondrodysplasia with a high incidence of Hirschsprung disease. This study suggests that Hirschsprung disease is associated especially with severe cartilage-hair hypoplasia: the patients with Hirschsprung disease had severe growth failure and a higher incidence of alopecia, infections, malignancies, and childhood anemia than the patients with cartilage-hair hypoplasia who did not have Hirschsprung disease.