Intervertebral Disc
Manoj Ramachandran, Tom Nunn in Basic Orthopaedic Sciences, 2018
The role of genetic predisposition is being increasingly recognized as a risk factor. Patients who are diagnosed with herniated discs before the age of 21 years are four to five times more likely to have a significant family history of disc herniation and similar magnetic resonance imaging (MRI) disc degeneration appearances have been noted in monozygotic twins. Genetic variations exist in the degree of synthesis and breakdown of structural components of the disc. Collagen IX encoding genes (COL9A2, COL9A3), genes encoding type I collagen (COL1A1-Sp1 binding site), Sox 9 (regulates the genes for aggrecan), vitamin D receptor gene and matrix metalloproteinase (MMP)-3 gene are some of those being studied for possible association with disc degeneration.
Genetic disorders, skeletal dysplasias and malformations
Ashley W. Blom, David Warwick, Michael R. Whitehouse in Apley and Solomon’s System of Orthopaedics and Trauma, 2017
The most common inheritance pattern is autosomal dominant, but there is a less common and clinically distinct autosomal recessive form. The majority of individuals affected with dominant MED have mutations of the COMP (cartilage oligomeric protein) gene, with approximately 10% presenting with abnormalities of the MATN3 gene, both affecting matrix production and causing abnormalities of the physical and material properties of joint cartilage. Mutations of COL9A1, COL9A2 and COL9A3 are uncommon and cause accumulation of type IX collagen and also lead to abnormalities of articular cartilage.
Orthogenomics
Kohlstadt Ingrid, Cintron Kenneth in Metabolic Therapies in Orthopedics, Second Edition, 2018
Candidate gene studies have uncovered different genes encoding for proteins that confer an increased susceptibility of hip or knee OA across a variety of molecular mechanisms. Examples are Wnt (wingless) cell signaling (FRZG) (26); extracellular proteins involved in cartilage anabolism (COL2 A1, COL9A2, COL1A1, COL1A2 and COMP (27–31) and catabolism (MMP-3 and ADAMTS-5) (32, 33); programmed cell death (FAS and TNF) (34); as well as mitochondrial apoptosis (ANP32A) (35), alterations in estrogen receptor status (36) and vitamin D metabolism (GC, VDR) (37).
Severe foveal hypoplasia and macular degeneration in Stickler syndrome caused by missense mutation in COL2A1 gene
Published in Ophthalmic Genetics, 2022
Mamika Asano, Katsuhiko Yokoyama, Kazuma Oku, Itsuka Matsushita, Kenichi Kimoto, Toshiaki Kubota, Hiroyuki Kondo
Mutations in the procollagen genes, COL2A1, COL11A1, COL11A2, COL9A1, COL9A2 and COL9A3 cause Stickler syndrome, and the COL2A1, COL11A1 and COL11A2 genes are responsible for autosomal dominant Stickler syndrome (4). Mutations in the COL2A1 gene are the most common cause of Stickler syndrome, and more than 80% of the mutations are truncation mutations, i.e., nonsense, insertion, deletion, and splicing mutations that lead to haploinsufficiency (Human Gene Mutation Database, HGMD; https://my.qiagendigitalinsights.com/bbp/view/hgmd/pro/start.php). Patients with truncation mutations in the COL2A1 gene show characteristic membranous structures in the vitreous (5,6). On the other hand, some of the missense mutations in the COL2A1 gene have been reported to cause specific alterations of the vitreous due to dominant-negative effects (5). As best we know, there are no reports on whether eyes with missense mutations have specific retinal findings.
Combined X-linked familial exudative vitreoretinopathy and retinopathy of prematurity phenotype in an infant with mosaic turner syndrome with ring X chromosome
Published in Ophthalmic Genetics, 2023
Sandra Hoyek, Marlene Wang, Audina M. Berrocal, Ashley Wong, Emily M. Place, Heather Mason-Suares, Angela E. Lin, Shizuo Mukai, Nimesh A. Patel
Since the phenotype was atypical for ROP, genetic testing using a 24-gene panel of inherited vitreoretinopathies was ordered. This is a targeted, next-generation sequencing (NGS) panel with sequencing and copy number analysis of 24 genes associated with inherited vitreoretinopathies (11). These genes included ATOH7, BEST1, CAPN5, COL11A1, COL11A2, COL18A1, COL2A1, COL9A1, COL9A2, COL9A3, CTC1, CTNNB1, FZD4, KCNJ13, KIF11, LRP5, NDP, NR2E3, P3H2, RCBTB1, RS1, TSPAN12, VCAN and ZNF408. Testing was performed on DNA extracted from peripheral blood.
High Myopia and Strabismus Induced by a Deep Intronic Mutation in COL2A1
Published in Current Eye Research, 2021
Shirel Rossenwasser-Weiss, Naama Orenstein, Alon Zahavi, Nitza Goldenberg-Cohen
Stickler syndrome is a connective tissue disorder of fibrillar collagen with an estimated prevalence of 1 in 7,500–9,000 neonates. It is inherited in both an autosomal dominant and autosomal recessive mode with phenotypically overlapping characteristics.1 Pathogenic variants COL2A1, COL11A1, or COL11A2 are inherited in an autosomal dominant manner; Stickler syndrome caused by pathogenic variants in COL9A1, COL9A2, or COL9A3 is inherited in an autosomal recessive manner.2–4