Genetic analysis and serum level of cartilage oligomeric matrix protein in patients with pseudoachondroplasia

Background Pseudoachondroplasia （PSACH） is an autosomal-dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein （COMP）.Clinical diagnosis of PSACH is based primarily on family history, physical examination, and radiographic evaluation.There is evidence that decreased serum COMP concentration may serve as a diagnostic marker in PSACH.Here, we investigated the role of this gene and the serum COMP concentration in Chinese patients with PSACH.Methods A family with three patients and a sporadic case were recruited.Genomic and phenotypic data were recorded.The diagnosis of PSACH was made on the base of clinical evaluation.The genomic DNA was extracted from peripheral blood leukocytes.The 8-19 exons and flanking intron-exon boundary sequences of COMP were amplified by polymerase chain reaction （PCR） and screened for mutation by direct DNA sequencing.Serum COMP concentrations of 4 patients and age-compatible control group of 20 unrelated healthy subjects were analyzed on the basis of an ELISA Kit for human cartilage oligomeric matrix protein.Results A deletion （c.1447-1455del） was identified in exon 13 in the sporadic case.The mean serum COMP concentrations of four patients （3.12±2.28） were significantly lower than those of control group （10.86±2.21, P 〈0.05）.There was no overlap in the distribution of serum COMP concentration between PSACH patients and controls.Conclusions Mutations in COMP gene are responsible for the PSACH.Serum COMP concentration may be suggested as an additional diagnostic marker to aid clinical findings in suspected cases of PSACH.

Gene mapping of autosomal dominant retinitis pigmentosa in a Chinese family

Background The autosomal dominant form of retinitis pigmentosa （ADRP） can be caused by mutations in 14 genes and further loci remains to be identified. This study was intended to identify mutations in a Chinese pedigree with ADRP. Methods A large Chinese family with retinitis pigmentosa was collected. The genetic analysis of the family suggested an autosomal dominant pattern. Microsatellite （STR） markers tightly linked to genes known to be responsible for ADRP were selected for linkage analysis. Exons along with adjacent splice junctions of PRPF31 were amplified by polymerase chain reaction （PCR） and screened by direct sequencing. Results The caused gene of ADRP was mapped to 19q13.4 between markers D19S572 and D19S877, with a maximum LOD score of 3.01 at marker D19S418 （recombination fraction=0）. Conclusion The affected gene linked to the 19q13.4 in a Chinese family with ADRP, which is different from other mutations at the same loci in other Chinese families.

EDM1： a novel point mutation in cartilage oligomeric matrix protein gene in a Chinese family with multiple epiphyseal dysplasia

Background Multiple epiphysis dysplasia （MED） is a common skeletal dysplasia with a significant locus heterogeneity. In the majority of clinically defined.cases, mutations have been identified in the gene encoding cartilage algometric matrix protein （ COMP）. Methods Five patients were included in the study. Linkage analysis and mutation analysis of the COMP gene were conducted in the patients and their family members. Results We have identified a novel mutation in axon 14 of COMP gene in the family. Conclusions This mutation produced a severe MED phenotype with marked short stature, early onset osteoarthritis, and remarkable radiographic changes. Our results extended the range of disease-causing mutations in COMP gene and contributed more information about relationship between mutations and phenotype.