title: Mutation Update for COL2A1 Gene Variants Associated with Type II Collagenopathies.
abstract: Mutations in the COL2A1 gene cause a spectrum of rare autosomal-dominant conditions characterized by skeletal dysplasia, short stature, and sensorial defects. An early diagnosis is critical to providing relevant patient care and follow-up, and genetic counseling to affected families. There are no recent exhaustive descriptions of the causal mutations in the literature. Here, we provide a review of COL2A1 mutations extracted from the Leiden Open Variation Database (LOVD) that we updated with data from PubMed and our own patients. Over 700 patients were recorded, harboring 415 different mutations. One-third of the mutations are dominant-negative mutations that affect the glycine residue in the G-X-Y repeats of the alpha 1 chain. These mutations disrupt the collagen triple helix and are common in achondrogenesis type II and hypochondrogenesis. The mutations resulting in a premature stop codon are found in less severe phenotypes such as Stickler syndrome. The p.(Arg275Cys) substitution is found in all patients with COL2A1-associated Czech dysplasia. LOVD-COL2A1 provides support and potential collaborative material for scientific and clinical projects aimed at elucidating phenotype-genotype correlation and differential diagnosis in patients with type II collagenopathies.
authors.affiliation: Laboratory of Rare and Autoinflammatory Diseases, CHRU, Montpellier, France.|Genetics & Immunopathology of Inflammatory Osteoarticular Diseases, INSERM UMR1183, Montpellier, France.
authors.forename: Mouna
authors.initials: M
authors.lastname: Barat-Houari
authors.affiliation: Laboratory of Rare and Autoinflammatory Diseases, CHRU, Montpellier, France.|Genetics & Immunopathology of Inflammatory Osteoarticular Diseases, INSERM UMR1183, Montpellier, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sarrabay
authors.affiliation: Laboratory of Rare and Autoinflammatory Diseases, CHRU, Montpellier, France.|University of Montpellier, Montpellier, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Gatinois
authors.affiliation: Laboratory of Rare and Autoinflammatory Diseases, CHRU, Montpellier, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Fabre
authors.affiliation: Laboratory of Rare and Autoinflammatory Diseases, CHRU, Montpellier, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Dumont
authors.affiliation: Genetics & Immunopathology of Inflammatory Osteoarticular Diseases, INSERM UMR1183, Montpellier, France.|University of Montpellier, Montpellier, France.|Department of Medical Genetics, Reference Center for Developmental Abnormalities and Constitutional Bone Diseases, CHRU, Montpellier, France.
authors.forename: David
authors.initials: D
authors.lastname: Genevieve
authors.affiliation: Laboratory of Rare and Autoinflammatory Diseases, CHRU, Montpellier, France.|Genetics & Immunopathology of Inflammatory Osteoarticular Diseases, INSERM UMR1183, Montpellier, France.|University of Montpellier, Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Touitou
mesh_terms: D024043:Collagen Type II / Q000235:genetics*; D030541:Databases, Genetic; D005799:Genes, Dominant; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D009154:Mutation; D010009:Osteochondrodysplasias / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II
keywords: COL2A1; LOVD; skeletal dysplasia; type II collagenopathies