{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T05:53:17Z","timestamp":1698213197124},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,6,7]],"date-time":"2005-06-07T00:00:00Z","timestamp":1118102400000},"content-version":"vor","delay-in-days":4526,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Med. Genet."],"published-print":{"date-parts":[[1993,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in the genes coding for the pro\u03b11 and pro\u03b12 chains of type I procollagen have been found in many patients with osteogenesis imperfecta (OI), a heritable disorder of connective tissue. The severity of the disease varies between families and even among members of the same family. This phenotypic variability covers a spectrum extending from very mild forms that cannot be easily detected to perinatally lethal forms. One explanation for this phenotypic variability is the nature of the mutation in the type I procollagen genes. Another explanation is mosaicism. Here we report on 2 families with propositi who have OI, whereas their mothers had a milder form of the disease. In one family, the molecular defect was previously shown to be a substitution of \u03b11<jats:sup>904<\/jats:sup> by cysteine [Constantinou et al., 1990]. The biochemical phenotype was characterized by significant post\u2010translational over modification of the mutated type 1 collagen molecules which also had a 3\u20134\u00b0C decrease in their thermal unfolding. Also, secretion of the procollagen into the culture media was delayed. In the second family, the proposita's muscle fibroblasts synthesized and secreted type I procollagen molecules that were highly over\u2010modified along the entire length of their triple\u2010helical domain. Cells from the mother also synthesized normal and over\u2010modified protein, although the amount of over\u2010modified protein was less than that synthesized by her daughter's cells. The exact molecular defect has not yet been defined.<\/jats:p><jats:p>The simplest explanation for the phenotypic variability seen within these 2 families is that the mothers of the propositi are mosaic for their respective mutations so that not all of their somatic cells produce abnormal type I procollagen. Hence, one additional explanation for the phenotypic variability in OI is the abundance of the mutated allele or the degree of mosaicism in the patient's population of cells so that the first affected individual in a family may be mildly affected by a mutation which in a heterozygous form is potentially lethal in his or her offspring.<\/jats:p>","DOI":"10.1002\/ajmg.1320450218","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T16:39:13Z","timestamp":1118507953000},"page":"246-251","source":"Crossref","is-referenced-by-count":13,"title":["Somatic cell mosaicism: Another source of phenotypic heterogeneity in nuclear families with osteogenesis imperfecta"],"prefix":"10.1002","volume":"45","author":[{"given":"C. D.","family":"Constantinou\u2010Deltas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger L.","family":"Ladda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darwin J.","family":"Prockop","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,6,7]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00291667"},{"key":"e_1_2_1_3_1","first-page":"237","article-title":"Perinatal lethal osteogenesis imperfecta (OI type II): A biochemically heterogeneous disorder usually due to new mutations in the genes for type I collagen","volume":"42","author":"Byers PH","year":"1988","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(90)90235-X"},{"key":"e_1_2_1_5_1","first-page":"591","article-title":"Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a dominant mutation in a human type I collagen gene (COL1A1)","volume":"46","author":"Cohn DH","year":"1990","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113920"},{"key":"e_1_2_1_7_1","first-page":"979","article-title":"A mutation in a type I procollagen gene on chromosome 17q21.31\u2010q22.05 or 7q21.3\u2010q22.1 that decreass the thermal stability of the protein in a woman with ankylosing spondylitis and osteopenia. Human Gene Mapping 10 (1989) Tenth International Workshop on Human Gene Mapping","volume":"51","author":"Constantinou CD","year":"1989","journal-title":"Cytogenet Cell Genet"},{"key":"e_1_2_1_8_1","first-page":"670","article-title":"Phenotypic heterogeneity in osteogenesis imperfecta. The mildly affected mother of a proband with a lethal variant has the same mutation substituting cysteine for \u03b11\u2010glycine 904 in a type procollagen gene (COL1A1)","volume":"47","author":"Constantinou CD","year":"1990","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_9_1","doi-asserted-by":"crossref","first-page":"9056","DOI":"10.1016\/S0021-9258(19)84487-3","article-title":"The molecular defect in an autosomal dominant form of osteogenesis imperfecta. Synthesis of type I procollagen containing cysteine in the triple\u2010helical domain of pro\u03b1 1(I) chains","volume":"261","author":"de Vries WN","year":"1986","journal-title":"J Biol Chem"},{"key":"e_1_2_1_10_1","series-title":"UCLA Symposium on Molecular Biology and Cellular Biology, New Series Vol. 46","first-page":"56","volume-title":"Cysteine in \u03b11 chains of human type I collagen produces a clinically heterogeneous form of osteogenesis imperfecta","author":"de Vries WN","year":"1987"},{"key":"e_1_2_1_11_1","doi-asserted-by":"crossref","unstructured":"EngelJ ProckopDJ(1990) The zipper\u2010like folding of collagen triple\u2010helices and the effects of mutations that disrupt the zipper.Ann Rev Biophys and Biophys Chem. (in press)","DOI":"10.1146\/annurev.bb.20.060191.001033"},{"key":"e_1_2_1_12_1","first-page":"355","article-title":"Review and hypothesis: Somatic mosaicism: Observations related to clinical genetics","volume":"43","author":"Hall JG","year":"1988","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_13_1","first-page":"857","article-title":"Genomic imprinting: Review and relevance to human diseases","volume":"46","author":"Hall JG","year":"1990","journal-title":"Am J Hum"},{"key":"e_1_2_1_14_1","doi-asserted-by":"crossref","unstructured":"KuivaniemiH TrompG ProckopDJ(1991) Mutations in collagen genes. Causes of rare and some common diseases in man.FASEB J. (in press)","DOI":"10.1096\/fasebj.5.7.2010058"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(73)90331-X"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(90)90181-5"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-9065-8_2"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/03008208909050002"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.16.2.101"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90856-1"},{"key":"e_1_2_1_21_1","first-page":"A237","article-title":"Substitution of serine for glycine \u03b12\u2013661 in the gene for type I procollagen (COL1A2) as a cause for post\u2010menopausal osteoporosis","volume":"47","author":"Spotila LD","year":"1990","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114286"},{"key":"e_1_2_1_23_1","first-page":"1034","article-title":"Variable expression of osteogenesis imperfecta in a nuclear family is explained by somatic mosaicism for a lethal point mutation in the \u03b1 1(I) gene (COL1A1) of type I collagen in a parent","volume":"46","author":"Wallis GA","year":"1990","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(86)90068-0"}],"container-title":["American Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.1320450218","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.1320450218","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T19:46:06Z","timestamp":1698176766000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.1320450218"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,1,15]]},"references-count":23,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1993,1,15]]}},"alternative-id":["10.1002\/ajmg.1320450218"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.1320450218","archive":["Portico"],"relation":{},"ISSN":["0148-7299","1096-8628"],"issn-type":[{"value":"0148-7299","type":"print"},{"value":"1096-8628","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,1,15]]}}}