A novel COMP mutation in a pseudoachondroplasia family of Chinese origin
1 National Center for Birth Defects Monitoring, West China Second University Hospital, Sichuan University, 20 Ren Min Nan Lu Section 3, Chengdu 610041, China
2 Department of Pediatrics, West China Second University Hospital, Sichuan University, 20 Ren Min Nan Lu Section 3, Chengdu 610041, China
3 National office for Maternal and Child Health Surveillance, West China Second University Hospital, Sichuan University, 20 Ren Min Nan Lu Section 3, Chengdu 610041, China
4 Yale University School of Public Health, 60 College street, New Haven, CT 06520, USA
BMC Medical Genetics 2011, 12:72 doi:10.1186/1471-2350-12-72Published: 21 May 2011
Pseudoachondroplasia (PSACH) is caused exclusively by mutations in the gene for cartilage oligomeric matrix protein (COMP). Only a small number of studies have documented the clinical phenotype and genetic basis in Chinese PSACH patients.
We investigated a four-generation PSACH pedigree of Chinese Han origin. Two patients and two unaffected individuals were recruited for clinical evaluation and molecular genetic analysis. The genomic DNA was extracted from peripheral blood leukocytes. Polymerase chain reaction (PCR) was adopted to amplify the 8-19 exons of COMP gene. Then the products were sequenced bi-directionally for screening mutation. Clinical evaluation revealed that PSACH patients in this pedigree had a severe disproportionate short stature (-10SD). A heterozygous TGTCCCTGG insertion in exon 13, between nucleotide 1352T and 1353G, were identified in the patients except the unaffected individuals, which resulted in a three-amino-acid insertion (451V_452P ins VPG) in the sixth calmodulin-like repeat of the COMP protein.
This c. 1352_1353ins TGTCCCTGG is a novel mutation responsible for severe familial PSACH.