A Novel COMP Mutated Allele Identified in a Chinese Family with Pseudoachondroplasia

Bing-Bing Guo,Lei Zeng,Zhuang-Zhuang Yuan,Rong Xiang,Jie-Yuan Jin,Burak Durmaz

doi:10.1155/2021/6678531

Abstract

Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia with an estimated incidence of ~1/60000 that is characterized by disproportionate short stature, brachydactyly, joint laxity, and early-onset osteoarthritis. COMP encodes the cartilage oligomeric matrix protein, which is expressed predominantly in the extracellular matrix (ECM) surrounding the cells that make up cartilage, ligaments, and tendons. Mutations in COMP are known to give rise to PSACH. In this study, we identified a novel nucleotide mutation (NM_000095.2: c.1317C>G, p.D439E) in COMP responsible for PSACH in a Chinese family by employing whole-exome sequencing (WES) and built the structure model of the mutant protein to clarify its pathogenicity. The novel mutation cosegregated with the affected individuals. Our study expands the spectrum of COMP mutations and further provides additional genetic testing information for other PSACH patients.

Highlights

Pseudoachondroplasia (PSACH, Online Mendelian Inheritance in Man (OMIM) 177170), whose incidence is estimated to be ~1/60000, is a relatively common osteochondrodysplasia
We enrolled a Chinese family with highly suspected PSACH (Figure 1(a))
(c.1317C>G, p.D439E) occurred at this amino acid (AA) site. By analyzing these three mutant protein models, we considered that D439N and D439G alter the electric charge of a Ca2+-binding site and that D439E breaks the spatial configuration of this binding region (Figure 2(c))

Summary

Introduction

Pseudoachondroplasia (PSACH, OMIM 177170), whose incidence is estimated to be ~1/60000 (http://www.orpha .net/), is a relatively common osteochondrodysplasia. The human COMP gene localizes on chromosome 19p13.1 and is a member of the thrombospondin gene family It contains 19 exons, encoding an amino-terminal coiled-coil oligomerization domain, four type II epidermal growth factorlike repeats (EGF-like), eight type 3 calmodulin-like repeats (CLRs/T3 repeats), and a globular carboxyl terminal domain (CTD). It is abundantly expressed in the extracellular matrix (ECM) surrounding the cells that make up cartilage, ligaments, synovium, and tendons. We detected a novel mutated allele in COMP (NM_000095.2: c.1317C>G, p.D439E) in a Chinese family diagnosed with highly suspected PSACH based on clinical and radiologic results. To the best of our knowledge, there have been no reports of this variant in previous studies that have not been presented in various single nucleotide polymorphism (SNP) databases

Materials and Methods

Results

Discussion

Conclusions

Conflicts of Interest