α1 type I collagen protein<unk>  is a group of genetic disorders, all of which cause bone fragility.<unk>  has high genetic heterogeneity, that is, many different genetic mutations lead to the same or similar sets of observable symptoms (phenotypes). The main causes for developing the disorder are a result of mutations in the COL1A1 and/or COL1A2 genes which are jointly responsible for the production of collagen type I. Approximately 90% of people with<unk>  are heterozygous for mutations in either the COL1A1 or COL1A2 genes. There are several biological factors that are results of the dominant form of<unk> . These factors include: intracellular stress; abnormal tissue mineralization; abnormal cell to cell interactions; abnormal cell-matrix interactions; a compromised cell matrix structure; and, abnormal interaction between non-collagenous proteins and collagen. Previous research lead to the belief that<unk>  was an autosomal dominant disorder with few other variations in genomes. However, with the lowering of the cost of DNA sequencing in the wake of 2003's Human Genome Project, autosomal recessive forms of the disorder have been identified. Recessive forms of<unk>  relate heavily to defects in the collagen chaperones responsible for production of procollagen and the assembly of the related proteins. Examples of collagen chaperones that are defective in patients with recessive forms of<unk>  include chaperone HSP47 (Cole-Carpenter syndrome) and FKBP65. Mutations in these chaperones result in an improper folding pattern in the collagen 1 proteins which causes the recessive form of the disorder. There are three significant types of<unk>  that are a result of mutations in the collagen prolyl 3-hydroxylation complex (components CRTAP, P3H1, and CyPB). These components are responsible for the modification of collagen α1(l)Pro986. Mutations in other genes such as SP7, SERPINF1, TMEM38B and BMP1 can also lead to irregularly formed proteins and enzymes that result in other recessive types of<unk> . Defects in the proteins pigment epithelium-derived factor (PEDF) and bone-restricted interferon-induced transmembrane protein (BRIL) are the causes of type V and VI<unk> . Defects in these proteins lead to defective bone mineralization which causes the characteristic brittle bones of<unk> . A single point mutation in the 5′ untranslated region (5′ UTR) of the IFITM5 gene, which encodes BRIL, is linked directly to<unk>  type V. In the rare case of type XIX, first discovered in 2016,<unk>  is inherited as an X-linked genetic disorder, with its detrimental effects resulting ultimately from a mutation in the gene MBTPS2. Genetic research is ongoing, and it is uncertain when all the genetic causes of<unk>  will be identified, as the number of genes that need to be tested to rule out the disorder continue to increase. In a study of 37 families, a 1.3% chance was found that<unk>  recurs in multiple siblings born to two unaffected parents—this is a much higher rate than would be expected if all such recurrences were de novo. The cause is genetic mosaicism; that is, some of, or most of, the germ cells of one parent have a dominant form of<unk> , but not enough of their somatic cells do to cause symptoms or obvious disability in the parent—the parent's different cells have two (or more) sets of slightly different DNA. It has been clinically observed that ≈5–10% of cases of<unk>  types II and III are attributable to genetic mosaicism.
Osteogenesis imperfecta
Lhermitte's sign
Dentinogenesis imperfecta
Cleidocranial dysostosis
Gerodermia osteodysplastica
Kyrle disease
Rhizomelic chondrodysplasia punctata
Acrodysostosis