Functional characterization of a rare pathogenic variant c.875G > A, p.(Cys292Tyr) in COMP.
Ann Hum Genet
; 87(5): 241-247, 2023 09.
Article
en En
| MEDLINE
| ID: mdl-37461830
ABSTRACT
BACKGROUND:
The protein encoded by the cartilage oligomeric matrix protein (COMP) gene is a noncollagenous extracellular matrix (ECM) protein that is important for chondrocyte formation and growth. Variations in the COMP gene cause pseudoachondroplasia (PSACH), which is mainly characterized by short-limbed dwarfing in the clinic.AIMS:
To characterize the function of a rare pathogenic variant in the COMP gene (c.875G > A, p.Cys292Tyr). MATERIALS &METHODS:
We performed 3D structural analysis, in vitro expression analysis, and immunofluorescence to characterize the effects of the variant on protein structure, expression, and cellular localization respectively.RESULTS:
Variation modeling showed that the interactions between amino acids were changed after the variation, and there were 31 changes in the secondary structure of mutant COMP (MT-COMP). Western blot showed that the intracellular quantity of MT-COMP was higher than the wild-type COMP (WT-COMP). Cellular immunofluorescence results showed that WT-COMP was less abundant and homogenously distributed in cells, while the MT-COMP accumulated in the cytoplasm.DISCUSSION:
Herein, we report a variant of COMP in a Chinese family with PSACH. We have shown that the rare missense variant, COMP c.875G > A, previously reported in ClinVar and identified in our patient, results in excessive accumulation of mutant protein in the cytoplasm, and is therefore pathogenic.CONCLUSION:
Through in silico and experimental analyses, we provide evidence that COMP c.875G > A is the likely cause of PSACH in a Chinese family.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Acondroplasia
Límite:
Humans
Idioma:
En
Revista:
Ann Hum Genet
Año:
2023
Tipo del documento:
Article
País de afiliación:
China