Table 2.
Major ECM components involved in genetic disorders
| Molecule name | Gene name(s)* | Phenotype(s)†,‡ |
|---|---|---|
| Fibril-forming collagens | ||
| Collagen I | COL1A1, COL1A2 | Caffey disease (COL1A1); Ehlers-Danlos syndrome; osteogenesis imperfecta |
| Collagen II | COL2A1 | Achondrogenesis; avascular necrosis of the femoral head; Czech dysplasia; Kniest dysplasia; Legg-Calve-Perthes disease; multiple epiphyseal dysplasia with myopia and deafness; osteoarthritis with mild chondrodysplasia; otospondylomegaepiphyseal dysplasia; platyspondylic skeletal dysplasia; spondyloepimetaphyseal dysplasia; spondyloepiphyseal dysplasia; spondyloperipheral dysplasia; Stickler syndrome; vitreoretinopathy with phalangeal epiphyseal dysplasia |
| Collagen III | COL3A1 | Ehlers-Danlos syndrome |
| Collagen V | COL5A1, COL5A2 | Ehlers-Danlos syndrome |
| Collagen XI | COL11A1, COL11A2 | Fibrochondrogenesis; Marshall syndrome (COL11A1); non-syndromic hearing loss (COL11A2); otospondylomegaepiphyseal dysplasia (COL11A2); Stickler syndrome; Weissenbacher-Zweymueller syndrome (COL11A2) |
| Network-forming collagens | ||
| Collagen IV | COL4A1–COL4A6 | Alport syndrome (COL4A3–COL4A5); benign familial hematuria (COL4A3, COL4A4); brain small vessel disease with Axenfeld-Rieger anomaly (COL4A1); brain small vessel disease with haemorrhage (COL4A1); diffuse leiomyomatosis with Alport syndrome (COL4A6); hereditary angiopathy with nephropathy, aneurysms and muscle cramps (COL4A1); porencephaly (COL4A1, COL4A2) |
| Collagen VIII | COL8A2 | Fuchs endothelial corneal dystrophy; posterior polymorphous corneal dystrophy |
| Collagen X | COL10A1 | Schmid-type metaphyseal chondrodysplasia |
| Beaded filament–forming collagens | ||
| Collagen VI | COL6A1–COL6A3 | Bethlem myopathy; myosclerosis (COL6A2); Ullrich congenital muscular dystrophy |
| Anchoring fibrils | ||
| Collagen VII | COL7A1 | Epidermolysis bullosa dystrophica; toenail dystrophy; transient bullous of the newborn |
| Fibril-associated collagens with interrupted triple helices | ||
| Collagen IX | COL9A1–COL9A3 | Multiple epiphyseal dysplasia; Stickler syndrome (COL9A1, COL9A2) |
| Transmembrane collagens and collagen-like proteins | ||
| Collagen XVII | COL17A1 | Junctional epidermolysis bullosa |
| Ectodysplasin A | EDA | Hypohidrotic ectodermal dysplasia; selective tooth agenesis |
| MSR1 | MSR1 | Barrett oesophagus; hereditary prostate cancer |
| PSPs | SFTPA2 | Idiopathic pulmonary fibrosis |
| Endostatin-producing collagens | ||
| Collagen XVIII | COL18A1 | Knobloch syndrome |
| Elastin and microfibrillar proteins | ||
| Elastin | ELN | Cutis laxa; supravalvular aortic stenosis |
| Fibrillins | FBN1, FBN2 | Acromicric dysplasia (FBN1); distal arthrogryposis (FBN2); geleophysic dysplasia (FBN1); isolated ectopia lentis (FBN1); Marfan syndrome (FBN1); MASS syndrome (FBN1); Shprintzen-Goldberg syndrome (FBN1); stiff skin syndrome (FBN1); Weill-Marchesani syndrome (FBN1) |
| Fibulins | EFEMP1, EFEMP2, FBLN1, FBLN5 | Age-related macular degeneration (FBLN5); cutis laxa (EFEMP2, FBLN5); Doyne honeycomb retinal dystrophy (EFEMP1); synpolydactyly (FBLN1) |
| Non-collagenous glycoproteins | ||
| Fibronectin | FN1 | Glomerulopathy with fibronectin deposits; plasma fibronectin deficiency |
| Laminins | LAMA2, LAMA3, LAMB2, LAMB3, LAMC2, LAMC3 | Cortical malformations, occipital (LAMC3); generalized atrophic benign epidermolysis bullosa (LAMA3); junctional epidermolysis bullosa (LAMA3, LAMB3, LAMC2); laryngoonychocutaneous syndrome (LAMA3); merosin-deficient muscular dystrophy (LAMA2); nephrotic syndrome (LAMB2); Pierson syndrome (LAMB2) |
| Tenascins | TNXB | Ehlers-Danlos syndrome, hypermobility type; Ehlers-Danlos-like syndrome due to tenascin-X deficiency |
| Thrombospodins | COMP | Multiple epiphyseal dysplasia; pseudoachondroplasia |
| Matrilins | ||
| Matrilins | MATN3 | Multiple epiphyseal dysplasia; spondyloepimetaphyseal dysplasia |
| Basement membrane proteoglycans | ||
| Bamacan | SMC3 | Cornelia de Lange syndrome |
| Perlecan | HSPG2 | Dyssegmental dysplasia; Schwartz-Jampel syndrome |
| Hyalectans (lecticans) | ||
| Aggrecan | ACAN | Osteochondritis dissecans, short stature and early-onset osteoarthritis; spondyloepimetaphyseal dysplasia; spondyloepiphyseal dysplasia |
| Versican | VCAN | Wagner syndrome |
| Small leucine-rich proteoglycans | ||
| Decorin | DCN | Stromal corneal dystrophy |
| Keratocan | KERA | Cornea plana |
| Nyctalopin | NYX | Stationary night blindness |
ECM, extracellular matrix.
*
Human gene names are listed.
†
Mutations that contribute to susceptibility to multifactorial diseases or infection or to ‘non-diseases’ are excluded.
‡
Data were extracted from the Online Mendelian Inheritance in Man resource (http://omim.org) (accessed 18 August 2012) (Hamosh et al. 2005).