A novel deleterious mutation in the COMP gene that causes pseudoachondroplasia

Abstract

Pseudoachondroplasia (PSACH) is a rare and severe genetic disease; therefore, an accurate molecular diagnosis is essential for appropriate disease treatment and family planning. Currently, the diagnosis of PSACH is based mainly on family history, physical examination and radiographic evaluation. Genetic studies of patients with PSACH in Chinese populations have been very limited. With the application of next-generation sequencing (NGS), a comprehensive molecular diagnosis of PSACH is now possible. The purpose of this study was to perform comprehensive NGS-based molecular diagnoses for patients with PSACH in China. We investigated the molecular genetics of one suspected PSACH family in this study. The DNA sample from the proband was sequenced using a custom capture panel that included 249 bone disease genes. Variant calls were filtered and annotated using an in-house automated pipeline. Then, we confirmed the variants by Sanger sequencing in three family members. After co-segregation analysis, the variant, c.1160_1162del of the COMP gene, was identified as a novel mutation responsible for this spontaneous form of PSACH.

Shoulder arthroplasty in dwarfism: A case report of pseudoachondroplasia with 17-year follow-up

“…18,19,21 These complications include humeral loosening, baseplate failure, scapular notching, and dislocation. 3,21 In the present case, the patient's pain levels necessitated a job change to reduce the burden of powering the wheelchair with her arms over long distances. Pain and function improved as her circumstances changed.…”

“…This results in calcium-binding and protein export dysfunction which ultimately triggers chondrocyte death during linear growth. 1,3 The classic manifestations of PSACH include abnormalities in the long bones, joints and spine. Clinical findings include early-onset osteoarthritis, ligamentous laxity, genu valgum, and bowing deformities of the lower extremity.…”

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

“…Thus, the domain is a mutation hot spot, where the COMP mutation we identified was located. In addition to a large number of missense mutations, it also includes in-frame small deletions, insertions, or indels [ 12 , 26 , 27 ]. Three COMP mutations (c.1315G>A, p.D439N; c.13169r, p.D439G; c.1317C>A, p.D439E) were identified in MED cases, which altered the 439 th amino acid (AA) of COMP[ 20 , 28 , 29 ].…”

“…Moreover, the boundary between PSACH and MED is indefinite. Recently, with the application of next-generation sequencing techniques, such as WES, the discovery of the genetic pathogenetic factor of individuals in heterogeneous conditions has facilitated the diagnosis of skeletal disorder disease, and it is also a powerful and cost-efficient method to verify the causative gene [ 13 , 26 ]. In the future, further efforts will be made to provide assistance in genetic counseling and disease prognosis.…”

Exome sequencing revealed a p.G299R mutation in the COMP gene in an Iranian family suffering from pseudoachondroplasia

“…detected a novel missense mutation C.1675 G>A in the COMP gene of four Chinese patients resulting in the substitution of lysine 559 with glutamate amino acid. In a recent study that covered the 249 genes of bone disorders, a novel deleterious c.1160_1162del of the COMP gene was found in a Chinese family suffering from PSACH using targeted next‐generation sequencing . Of note, citation of all of the available published articles that consider the association of COMP mutations and SS is impossible in this discussion, although a quick search in PubMed demonstrates how this area of interest has been enriched from 1995 to date.…”