• Mutations in the COL1A1 gene are associated with the following conditions: Ehlers-Danlos syndrome, vascular type: In rare cases, specific heterozygous arginine-to-cysteine substitution mutations in COL1A1 that are also associated with vascular fragility and mimic COL3A1-vEDS Ehlers-Danlos syndrome, arthrochalasia type: It is caused by mutations in the COL1A1 gene. (wikipedia.org)
  • de Wett W, Sippola M, Tromp G, Prockop D, Chu ML, Ramirez F , Use of R-loop mapping for the assessment of human collagen mutations. (coriell.org)
  • Mutations in this gene are associated with osteogenesis imperfecta, Ehlers-Danlos syndrome, and idiopathic osteoporosis. (thermofisher.com)
  • In osteogenesis imperfecta, synthesis of collagen, one of the normal components of bone, is impaired in most affected people because of mutations in the genes that play an important role in the development of collagen. (msdmanuals.com)
  • Background: Whereas mutations affecting the helical domain of type I procollagen classically cause Osteogenesis Imperfecta (OI), helical mutations near the amino (N)-proteinase cleavage site have been suggested to result in a mixed OI/Ehlers-Danlos syndrome (EDS)-phenotype. (amrita.edu)
  • The collagen defects result from dominant mutations, requiring only one copy of a mutant gene to cause bone disease. (nih.gov)
  • About one fourth of the known collagen mutations are lethal. (nih.gov)
  • Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. (smw.ch)
  • It is predominantly inherited in an autosomal dominant fashion and mutations affecting type I collagen, the main structural protein of the extracellular matrix of bone, skin, and other connective tissues are evident in over 90% of people with this disease. (kenkyugroup.org)
  • OI is relatively rare (1:20,000-50,000 live births) and mutations affecting type I collagen, the main structural protein of the extracellular matrix of bone, skin, and other connective tissues are evident in over 90% of people with the disease [2]. (kenkyugroup.org)
  • Achondrogenesis results from mutations in the TRIP11 (ACGIA), SLC26A2 (ACGIB), and COL2A1 (ACGII) genes, with achondrogenesis types IA and IB being autosomal recessive conditions and achondrogenesis type II most often being sporadic. (medscape.com)
  • In the late 1980s, structural mutations in collagen II were shown to cause achondrogenesis type II, which thus constitutes the severe end of the spectrum of collagen II chondrodysplasias. (medscape.com)
  • Classification of type IB as a separate group has been confirmed by the discovery of its association with mutations in the diastrophic dysplasia sulfate transporter ( DDST ) gene, making it allelic with diastrophic dysplasia. (medscape.com)
  • Type IB is caused by recessive mutations of the diastrophic dysplasia sulfate transporter gene ( SLC26A2 ), and type II is caused by autosomal dominant mutations of the type II collagen gene ( COL2A1 ). (medscape.com)
  • Several heritable osteochondrodysplasias have now been recognized as members of the family of type II collagen disorders, all of which result from dominant mutations in the COL2A1 gene. (medscape.com)
  • When Willow is born with severe osteogenesis imperfecta, her parents are devastated-she will suffer hundreds of broken bones as she grows, a lifetime of pain. (simonandschuster.com)
  • Bisphosphonates are widely used in the treatment of moderate to severe osteogenesis imperfecta, from infancy to adulthood. (smw.ch)
  • Montpetit K, Palomo T, Glorieux FH, Fassier F, Rauch F. Multidisciplinary Treatment of Severe Osteogenesis Imperfecta: Functional Outcomes at Skeletal Maturity. (smw.ch)
  • Campbell, B.G., Wootton, J.A.M., Macleod, J.N., Minor, R.R. : Canine COL1A2 mutation resulting in C-terminal truncation of pro-alpha 2(I) and severe osteogenesis imperfecta Journal of Bone & Mineral Research 16:1147-1153, 2001. (genomia.cz)
  • Collagen, type I, alpha 1, also known as alpha-1 type I collagen, is a protein that in humans is encoded by the COL1A1 gene. (wikipedia.org)
  • The COL1A1 gene produces a component of type I collagen, called the pro-alpha1(I) chain. (wikipedia.org)
  • This chain combines with another pro-alpha1(I) chain and also with a pro-alpha2(I) chain (produced by the COL1A2 gene) to make a molecule of type I procollagen. (wikipedia.org)
  • Because only one copy of the gene is directing the cell to make pro-alpha1(I) chains, cells from people with this disorder make only half of the normal amount of type I collagen, which results in bone fragility and other symptoms. (wikipedia.org)
  • Most kids with a collagen problem have it because they inherited a gene from one or both of their parents. (kidshealth.org)
  • In Type V, the variant is in the promoter region of the IFITM5 gene (11p15.5). (orpha.net)
  • This gene encodes an enzyme that is a member of the collagen prolyl hydroxylase family. (origene.com)
  • Reciprocal translocations between chromosomes 17 and 22, where this gene and the gene for platelet-derived growth factor beta are located, are associated with a particular type of skin tumor called dermatofibrosarcoma protuberans, resulting from unregulated expression of the growth factor. (thermofisher.com)
  • Mechanical stimulation led to a significant increase in chondrogenic gene expression, while histological analysis detected sulphated glycosaminoglycans and collagen II only in loaded specimens, confirming MC hydrogel suitability to support load induced MSCs chondrogenesis. (nature.com)
  • Next, Drs. Morello and Lee studied a family with an unexplained form of OI, learning that a partially functioning copy of the CRTAP gene accounted for a moderate form of the disease, designated type VII OI. (nih.gov)
  • This gene encodes the pro-alpha1 chains of type I collagen whose triple helix comprises two alpha1 chains and one alpha2 chain. (antikoerper-online.de)
  • Moreover, single-cell RT-PCR of type I collagen gene expression demonstrated higher expression on cells seeded on the nanofibers. (duke.edu)
  • This classification was based on the notion that "collagen" was equivalent to "connective tissue", but with the present recognition of the different types of collagen and the aggregates derived from them as distinct entities, the term "collagen diseases" now pertains exclusively to those inherited conditions in which the primary defect is at the gene level and affects collagen biosynthesis, post-translational modification, or extracellular processing directly. (lookformedical.com)
  • It is often caused by a defect in the gene that produces type I collagen, an important building block of bone. (medlineplus.gov)
  • Collagen is a protein that strengthens and supports many tissues in the body, including cartilage, bone, tendon, skin and the white part of the eye (sclera). (wikipedia.org)
  • When this part of the protein is missing, the structure of type I collagen is compromised. (wikipedia.org)
  • The altered protein interacts abnormally with other collagen-building proteins, disrupting the structure of type I collagen fibrils and trapping collagen in the cell. (wikipedia.org)
  • Collagen (KOL-uh-jin) is a protein in the body. (kidshealth.org)
  • Researchers at the National Institutes of Health have discovered that a previously unexplained fatal form of Osteogenesis Imperfecta - a disorder that weakens bones and which may cause frequent fractures - results from a genetic defect in a protein involved in the production of collagen. (nih.gov)
  • The function of CRTAP is not well understood, but it is known to be part of a complex of proteins involved in the chemical transformation of collagen from simple protein "chains" into its final form. (nih.gov)
  • Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta. (smw.ch)
  • We show that perichondrial cells, which express abundant type I procollagen, and growth plate chondrocytes, which were found to express low amounts of type I procollagen, had ER stress and dysregulation of the same unfolded protein response pathway as previously demonstrated in osteoblasts. (jci.org)
  • Osteogenesis imperfecta (OI) is a genetic bone disorder characterized by impaired production of type 1 collagen, an essential protein in the development and maintenance of bones and connective tissue. (osmosis.org)
  • Collagen is a protein that can help keep the skin looking smooth. (medicalnewstoday.com)
  • Collagen is the most abundant type of protein in the body and a key component of the skin. (medicalnewstoday.com)
  • This approach to the study of disease, referred to as "materiomics" by the lead researcher on the project, Professor Markus Buehler of MIT's Department of Civil and Environmental Engineering, could prove valuable in the study of other diseases - particularly collagen- and other protein-based diseases - where a material's behavior and breakdown play a critical role. (mit.edu)
  • He sees the application of this approach to collagen-based diseases as a starting point that could lead to a similar analysis of the mechanical properties of tissue involved in other protein-based diseases. (mit.edu)
  • Incorporation of hydroxyapatite (HA) in a collagen scaffold dramatically improves bone morphogenic protein (BMP) sequestration via biophysical interactions with BMP, thereby providing more controlled BMP release compared with pristine collagen. (lu.se)
  • Tissues that are rich in type I collagen, such as the skin, bones, and tendons, are affected by this change. (wikipedia.org)
  • These alterations negatively affect tissues that are rich in type I collagen, such as the skin, bones, teeth, and tendons, leading to the signs and symptoms of type III osteogenesis imperfecta. (wikipedia.org)
  • Most of it is type I collagen, found in bones and tendons. (kidshealth.org)
  • Patients with type II present multiple rib and long bone fractures at birth, marked deformities, broad long bones, low density on skull X-rays, and dark sclera. (orpha.net)
  • Osteogenesis imperfecta is a hereditary disorder that disrupts the proper formation of bones and makes bones abnormally fragile. (msdmanuals.com)
  • Most people with osteogenesis imperfecta have fragile bones, and about 50 to 65% have hearing loss. (msdmanuals.com)
  • This type causes bones to often break after very minor injuries, usually when children begin to walk. (msdmanuals.com)
  • Children with this type have bones that fracture easily during childhood before puberty. (msdmanuals.com)
  • Osteogenesis imperfecta (OI) or "brittle bone disease" is a congenital disorder in which a person is born with very brittle bones, usually due to either a complete lack of or incorrectly formed type I collagen. (hss.edu)
  • Collagen provides strength and support to the bones, and in individuals with OI, the collagen produced is weak, leading to bones that are brittle and prone to fractures. (osmosis.org)
  • Osteogenesis imperfecta (OI) is a spectrum of connective tissue disorders characterized by bones that break easily with little or no apparent cause. (kenkyugroup.org)
  • Collagen is a main part of connective tissue that connects and supports the whole body, including the bones. (lluch.org)
  • Disease causes a defect in Type 1 Collagen that leads to "brittle bones", meaning the patients have frequent fractures with little trauma. (nbmeanswers.com)
  • Both types have crenated ilia and stellate long bones. (medscape.com)
  • Type III has nonfractured ribs, halberd ilia, mushroom-stem long bones, and a CI femur of 2.8-4.9. (medscape.com)
  • Type IV has nonfractured ribs, sculpted ilia, well-developed long bones, and a CI femur of 4.9-8. (medscape.com)
  • This posteroanterior (PA) view radiograph of an infant with achondrogenesis type II shows the relatively large calvaria with normal cranial ossification, short and flared thorax, bell-shaped cage and shorter ribs without fractures, relatively well ossified iliac bone with long crescent-shaped medial and inferior margins, and short tubular bones. (medscape.com)
  • Osteogenesis imperfecta is a condition causing extremely fragile bones. (medlineplus.gov)
  • Sillence DO, Senn A, Danks D. Genetic heterogeneity in osteogenesis imperfecta. (smw.ch)
  • Owing to the lethality of OI type II, early prenatal diagnosis and genetic counseling is crucial to assist parents in making informed decisions relative to pregnancy termination. (kenkyugroup.org)
  • Osteogenesis imperfecta (OI) refers to a group of connective tissue disorders exhibiting both clinical and genetic heterogeneity that is characterized by qualitative and/or quantitative anomalies of collagen metabolism and manifests with increased bone fragility [1-3]. (kenkyugroup.org)
  • Osteogenesis imperfecta (OI) is a rare inherited (genetic) bone disorder that is present at birth. (lluch.org)
  • Another heart-wrenching, controversial novel by Jodi Picoult, Handle with Care introduces Willow, a smart and charming five-year-old who was born with a brittle bone disease called osteogenesis imperfecta. (simonandschuster.com)
  • Osteogenesis Imperfecta or OI is also referred to as the Brittle Bone Disease. (ihealthdirectory.com)
  • Osteogenesis imperfecta (OI), or brittle bone disease, is a disorder characterized by bone fragility and increased fracture incidence. (jci.org)
  • About 1 in 10,000 people are diagnosed with brittle bone disease annually, and defective collagen is implicated in many other medical conditions, including Alport syndrome (kidney disease) and Ehlers-Danlos syndrome (overly-flexible skin and joints). (mit.edu)
  • Aka "Brittle Bone Dz" aka Collagen Type I deficiency. (nbmeanswers.com)
  • In approximately 90% of cases, OI is caused by monoallelic variants in the COL1A1 and COL1A2 genes (17q21.33 and 7q21.3) encoding the alpha1 and alpha2 chains of type 1 collagen. (orpha.net)
  • The well-known forms of Osteogenesis Imperfecta (OI) result from a defect in the genes for type I collagen, which serves as a kind of molecular scaffolding that holds together bone, tendons, skin and other tissues. (nih.gov)
  • Because of the defect, there is not enough collagen. (lluch.org)
  • An ultra-low dose of BMP-2/7 delivered via a collagen-HA (CHA) scaffold leads to accelerated healing of a critical femoral defect in rats while a 20-times higher BMP-2 dose was required to achieve comparable results. (lu.se)
  • On November 17, 2021, Dr. Robert Sandhaus (pulmonologist and OIF Medical Advisory Council member) was joined by Admiral Rachel Levine, MD (Assistant Secretary of Health, US Department of Health and Human Services) to share COVID-19 vaccination news and guidelines for people with osteogenesis imperfecta. (oif.org)
  • Osteogenesis imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. (nih.gov)
  • OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. (nih.gov)
  • Note disproportionately short stature with mesomelic shortening and deformities of forearms and legs (in mesomelic dysplasia) and short forearms with Madelung-type deformity (in Leri-Weill syndrome). (medscape.com)
  • Type IV osteogenesis imperfecta ranges widely in severity and can cause deformities. (msdmanuals.com)
  • Disrupted growth plates and progressive deformities in osteogenesis imperfecta as a result of the substitution of glycine 585 by valine in the alpha 2 (I) chain of type I collagen. (bmj.com)
  • People with this type have many fractures starting very early in life and can have severe bone deformities. (medlineplus.gov)
  • After birth, doctors base the diagnosis of osteogenesis imperfecta on the symptoms and on a physical examination. (msdmanuals.com)
  • Methods: We performed biochemical and molecular analysis of type I (pro-) collagen in a cohort of seven patients referred with a clinical diagnosis of EDS and showing only subtle signs of OI. (amrita.edu)
  • Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment. (smw.ch)
  • Although fibroblast cell culture can detect collagen abnormalities in about 85% of patients, the diagnosis of OI practically relies on the distinctive clinical and radiographic picture. (kenkyugroup.org)
  • The most clinically relevant characteristic of all types of OI is bone fragility, which manifests as multiple spontaneous fractures. (orpha.net)
  • A family of structurally related collagens that form the characteristic collagen fibril bundles seen in CONNECTIVE TISSUE. (lookformedical.com)
  • Multiple rib fractures are characteristic of type I but not type II. (medscape.com)
  • Collagen type XI is heterotrimer containing alpha1(XI), alpha2(XI) and alpha3(XI) subunits. (lookformedical.com)
  • Children with this type may have increased risk of fractures during childhood. (msdmanuals.com)
  • Children with this type are very short and have curving of the spine and frequent fractures. (msdmanuals.com)
  • Osteogenesis imperfecta is an inherited connective tissue disease characterized by extreme bone fragility that leads to numerous fractures. (genomia.cz)
  • When compared to parental and control samples, skin fibroblasts of the proband synthesized two populations of type I collagen molecules. (wustl.edu)
  • His model incorporates a bottom-up description of collagen, accounting for the hierarchical assembly of molecules, each of which consists of three helical threads of amino acids. (mit.edu)
  • Using atomistic modeling, the researchers demonstrate exactly how the substitution of eight different amino acids in place of glycine changes the electrochemical behavior of the collagen molecules and affects the mechanical properties of the collagen tissue. (mit.edu)
  • Collagen type IV molecules assemble to form a sheet-like network which is involved in maintaining the structural integrity of basement membranes. (lookformedical.com)
  • Type I is mild and nondeforming with normal height or short stature, blue sclera, and no dentinogenesis imperfecta (DI). (orpha.net)
  • Type III is severe and the main signs include severe short stature, a triangular face, severe scoliosis, grayish sclera, and DI. (orpha.net)
  • Patients with type IV have moderate short stature, variable severity of scoliosis, grayish or white sclera, and some have DI. (orpha.net)
  • Type V is characterized by mild to moderate short stature, metaphyseal dysplasia at birth, dislocation of the radial head, mineralized interosseous membranes of the forearm and lower leg, hyperplastic callus (particularly when growth is more rapid e.g. during infancy or puberty), white sclera, and no DI. (orpha.net)
  • A vitamin C deficiency can lead to low collagen levels, resulting in a potentially serious condition known as scurvy. (medicalnewstoday.com)
  • Thus, allogeneic bone marrow transplantation can lead to engraftment of functional mesenchymal progenitor cells, indicating the feasibility of this strategy in the treatment of osteogenesis imperfecta and perhaps other mesenchymal stem cell disorders as well. (nih.gov)
  • They are found in many cell types and are involved in the maintenance and regulation of cell shape and behavior, including PLATELET ACTIVATION and aggregation, through many different signaling pathways and differences in their affinities for collagen isoforms. (lookformedical.com)
  • These variants can cause types I-IV of OI. (orpha.net)
  • Achondrogenesis type II, hypochondrogenesis, and neonatal spondyloepiphyseal dysplasia congenita are now known to be phenotypic variants of the same disorder. (medscape.com)
  • Currently, three variants of achondrogenesis have been defined based on radiologic and histopathologic features: type IA (Houston-Harris), type IB (Parenti-Fraccaro), and type II (Langer-Saldino). (medscape.com)
  • According to researchers at MIT, that minuscule encoding error creates a defective collagen molecule that, at the site of the amino acid substitution, repels rather than attracts the collagen molecule alongside it. (mit.edu)
  • These enzymes are localized to the endoplasmic reticulum and their activity is required for proper collagen synthesis and assembly. (origene.com)
  • Without the hydroxylation of lysine, by the enzyme lysyl hydroxylase, the final collagen structure cannot form. (wikipedia.org)
  • This discovery provides a basis for counseling families that have lost a child to this previously unexplained form of Osteogenesis Imperfecta," said Duane Alexander, Director of the NIH institute that conducted the study, the National Institute of Child Health and Human Development. (nih.gov)
  • Owing to its 100% case fatality rate, OI type II which has an incidence of 1-2/100,000 live births is the most severe form inevitably resulting to intrauterine or perinatal deaths. (kenkyugroup.org)
  • As age and other factors reduce collagen levels, the skin loses its elasticity, and lines can form. (medicalnewstoday.com)
  • Structure of native collagen confirmed by ability to form microfibrils. (mdbioproducts.com)
  • The alpha subunits of collagen type VI assemble into antiparallel, overlapping dimers which then align to form tetramers. (lookformedical.com)
  • Several forms of collagen type V exist depending upon the composition of the subunits that form the trimer. (lookformedical.com)
  • The severe form of type II OI can be seen on ultrasound when the fetus is as young as 16 weeks. (medlineplus.gov)
  • Type I, or mild OI, is the most common form. (medlineplus.gov)
  • Type II is a severe form that often leads to death in the first year of life. (medlineplus.gov)
  • There are other types of OI, but they occur very rarely and most are considered subtypes of the moderately severe form (type IV). (medlineplus.gov)
  • Infant with Beemer-type (left) and an infant with Majewski-type (right) short-rib syndrome (SRS). (medscape.com)
  • Child with Hurler syndrome (mucopolysaccharidosis type IH). (medscape.com)
  • USA 85: 5254 (1988)] found that the previously demonstrated shortened pro-alpha-2 chain of type I collagen resulted from deletion of exon 28 which in turn resulted from substitution of G for A at the 3-prime end of intron 27. (coriell.org)
  • The finding of a glycine substitution in a α1(I) chain of a patient with the milder type IV osteogenesis imperfecta phenotype requires modification of current molecular models for type II and IV osteogenesis imperfecta. (wustl.edu)
  • The following product was used in this experiment: Collagen V Alpha-1 Chain (VR domain) Monoclonal Antibody (6A7) from Thermo Fisher Scientific, catalog # 90009-100UG. (thermofisher.com)
  • There are at least 8 different types of the disease. (lluch.org)
  • Scholars@Duke publication: Growth of mesenchymal stem cells on electrospun type I collagen nanofibers. (duke.edu)
  • We reconstituted type I collagen nanofibers prepared by electrospin technology and examined the morphology, growth, adhesion, cell motility, and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (MSCs) on three nano-sized diameters (50-200, 200-500, and 500-1,000 nm). (duke.edu)
  • Collagen helps the skin cells renew and repair themselves. (medicalnewstoday.com)
  • Osteogenesis imperfecta can range from mild to severe. (msdmanuals.com)
  • Researchers suggested that achondrogenesis type III probably corresponds to type II and that type IV probably corresponds to mild type II (hypochondrogenesis). (medscape.com)