Case Report: Whole-exome sequencing identified two novel COMP variants causing pseudoachondroplasia

Lin Zhou; Jing Chen; Qian Liu; Shuting Yang; Wanqin Xie; Ying Peng

doi:10.3389/fendo.2023.1267946

Case Report: Whole-exome sequencing identified two novel COMP variants causing pseudoachondroplasia

Front Endocrinol (Lausanne). 2023 Nov 23:14:1267946. doi: 10.3389/fendo.2023.1267946. eCollection 2023.

Authors

Lin Zhou¹, Jing Chen¹, Qian Liu², Shuting Yang¹, Wanqin Xie³, Ying Peng¹

Affiliations

¹ Department of Medical Genetics, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China.
² Medical Department, Zhejiang Biosan Biochemical Technologies Co. Ltd, Hangzhou, Zhejiang, China.
³ National Health Commission Key Laboratory of Birth Defects for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China.

Abstract

Pseudoachondroplasia (PSACH) is a rare, dominant genetic disorder affecting bone and cartilage development, characterized by short-limb short stature, brachydactyly, loose joints, joint stiffness, and pain. The disorder is caused by mutations in the COMP gene, which encodes a protein that plays a role in the formation of collagen fibers. In this study, we present the clinical and genetic characteristics of PSACH in two Chinese families. Whole-exome sequencing (WES) analysis revealed two novel missense variants in the COMP gene: NM_000095.3: c.1319G>T (p.G440V, maternal) and NM_000095.3: c.1304A>T (p.D435V, paternal-mosaic). Strikingly, both the G440V and D435V mutations were located in the same T3 repeat motif and exhibited the potential to form hydrogen bonds with each other. Upon further analysis using Missense3D and PyMOL, we ascertained that these mutations showed the propensity to disrupt the protein structure of COMP, thus hampering its functioning. Our findings expand the existing knowledge of the genetic etiology underlying PSACH. The identification of new variants in the COMP gene can broaden the range of mutations linked with the condition. This information can contribute to the diagnosis and genetic counseling of patients with PSACH.

Keywords: case report; comp; novel missense variants; pseudoachondroplasia; whole-exome sequencing.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Achondroplasia* / genetics
Cartilage Oligomeric Matrix Protein* / genetics
Exome Sequencing
Humans
Matrilin Proteins / genetics
Osteochondrodysplasias* / genetics

Substances

Cartilage Oligomeric Matrix Protein
Matrilin Proteins
COMP protein, human

Supplementary concepts

Pseudoachondroplasia

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by The National Key Research and Development Program of China(grant no.2021YFC1005305),Major Scientific and Technological Projects for Collaborative Prevention and Control of Birth Defects in Hunan Province (grant no. 2019SK1013), the Science and Technology Foundation of Changsha City (grant no. kzd22049) and Project of Hunan Provincial Health Commission (grant no. C202301039196).