{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:11:01Z","timestamp":1761718261399},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2013,4,26]],"date-time":"2013-04-26T00:00:00Z","timestamp":1366934400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genet"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>\n              <jats:italic>COL11A1<\/jats:italic> is a large complex gene around 250 kb in length and consisting of 68 exons. Pathogenic mutations in the gene can result in Stickler syndrome, Marshall syndrome or Fibrochondrogenesis. Many of the mutations resulting in either Stickler or Marshall syndrome alter splice sites and result in exon skipping, which because of the exon structure of collagen genes usually leaves the message in-frame. The mutant protein then exerts a dominant negative effect as it co-assembles with other collagen gene products. To date only one large deletion of 40 kb in the <jats:italic>COL11A1<\/jats:italic>, which was detected by RT-PCR, has been characterized. However, commonly used screening protocols, utilizing genomic amplification and exon sequencing, are unlikely to detect such large deletions. Consequently the frequency of this type of mutation is unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Case presentations<\/jats:title>\n            <jats:p>We have used Multiplex Ligation-Dependent Probe Amplification (MLPA) in conjunction with exon amplification and sequencing, to analyze patients with clinical features of Stickler syndrome, and have detected six novel deletions that were not found by exon sequencing alone.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Exon deletions appear to represent a significant proportion of type 2 Stickler syndrome. This observation was previously unknown and so diagnostic screening of <jats:italic>COL11A1<\/jats:italic> should include assays capable of detecting both large and small deletions, in addition to exon sequencing.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2350-14-48","type":"journal-article","created":{"date-parts":[[2013,4,26]],"date-time":"2013-04-26T22:14:11Z","timestamp":1367014451000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Deletions within COL11A1in Type 2 stickler syndrome detected by multiplex ligation-dependent probe amplification (MLPA)"],"prefix":"10.1186","volume":"14","author":[{"given":"Raymon","family":"Vijzelaar","sequence":"first","affiliation":[]},{"given":"Sarah","family":"Waller","sequence":"additional","affiliation":[]},{"given":"Abdellatif","family":"Errami","sequence":"additional","affiliation":[]},{"given":"Alan","family":"Donaldson","sequence":"additional","affiliation":[]},{"given":"Teresa","family":"Lourenco","sequence":"additional","affiliation":[]},{"given":"Marcia","family":"Rodrigues","sequence":"additional","affiliation":[]},{"given":"Vivienne","family":"McConnell","sequence":"additional","affiliation":[]},{"given":"Gregory","family":"Fincham","sequence":"additional","affiliation":[]},{"given":"Martin","family":"Snead","sequence":"additional","affiliation":[]},{"given":"Allan","family":"Richards","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2013,4,26]]},"reference":[{"key":"1079_CR1","first-page":"433","volume":"40","author":"GB Stickler","year":"1965","unstructured":"Stickler GB, Belau PG, Farrell FJ, Jones JD, Pugh DG, Steinberg AG, Ward LE: Hereditary progressive arthro-ophthalmopathy. Mayo Clin Proc. 1965, 40: 433-455.","journal-title":"Mayo Clin Proc"},{"key":"1079_CR2","doi-asserted-by":"publisher","first-page":"6624","DOI":"10.1073\/pnas.88.15.6624","volume":"88","author":"NN Ahmad","year":"1991","unstructured":"Ahmad NN, Ala-Kokko L, Knowlton RG, Jimenez SA, Weaver EJ, Maguire JI, Tasman W, Prockop DJ: Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy). Proc Natl Acad Sci USA. 1991, 88: 6624-6627. 10.1073\/pnas.88.15.6624.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1079_CR3","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/0092-8674(95)90493-X","volume":"80","author":"M Vikkula","year":"1995","unstructured":"Vikkula M, Mariman ECM, Lui VCH, Zhidkova NI, Tiller GE, Goldring MB, van Beersum SE, de Waal Malefijt MC, van den Hoogen FH, Ropers HH: Autosomal dominant and recessive osteochondrodysplasias associated with the COL11A2 locus. Cell. 1995, 80: 431-437. 10.1016\/0092-8674(95)90493-X.","journal-title":"Cell"},{"key":"1079_CR4","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1093\/hmg\/5.9.1339","volume":"5","author":"AJ Richards","year":"1996","unstructured":"Richards AJ, Yates JRW, Williams R, Payne SJ, Pope FM, Scott JD, Snead MP: A family with Stickler syndrome type 2 has a mutation in the COL11A1 gene resulting in the substitution of glycine 97 by valine in \u03b11(XI) collagen. Hum Mol Genet. 1996, 5: 1339-1343. 10.1093\/hmg\/5.9.1339.","journal-title":"Hum Mol Genet"},{"key":"1079_CR5","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3109\/07853890109002055","volume":"33","author":"J Myllyharju","year":"2001","unstructured":"Myllyharju J, Kivirikko KI: Collagen and collagen-related diseases. Ann Med. 2001, 33: 7-21. 10.3109\/07853890109002055.","journal-title":"Ann Med"},{"key":"1079_CR6","doi-asserted-by":"publisher","first-page":"E461","DOI":"10.1002\/humu.21257","volume":"31","author":"AJ Richards","year":"2010","unstructured":"Richards AJ, McNinch A, Martin H, Oakhill K, Rai H, Waller S, Treacy B, Whittaker J, Meredith S, Poulson A, Snead MP: Stickler syndrome and the vitreous phenotype: mutations in COL2A1 and COL11A1. Hum Mut. 2010, 31: E461-E471.","journal-title":"Hum Mut"},{"key":"1079_CR7","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1086\/302585","volume":"65","author":"S Annunen","year":"1999","unstructured":"Annunen S, K\u00f6rkk\u00f6 J, Czarny M, Warman ML, Brunner HG, K\u00e4\u00e4ri\u00e4inen H, Mulliken JB, Tranebjaerg L, Brooks DG, Cox GF: Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall\/Stickler phenotypes. Am J Hum Genet. 1999, 65: 974-983. 10.1086\/302585.","journal-title":"Am J Hum Genet"},{"key":"1079_CR8","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1038\/sj.ejhg.5200377","volume":"7","author":"S Martin","year":"1999","unstructured":"Martin S, Richards AJ, Yates JRW, Scott JD, Pope FM, Snead MP: Stickler Syndrome: further mutations in COL11A1 and evidence for additional locus heterogeneity. Eur J Hum Genet. 1999, 7: 807-814. 10.1038\/sj.ejhg.5200377.","journal-title":"Eur J Hum Genet"},{"key":"1079_CR9","volume-title":"GeneReviews [internet]","author":"NH Robin","year":"2000","unstructured":"Robin NH, Moran RT, Warman M, Ala-Kokko L: Stickler syndrome. GeneReviews [internet]. Edited by: Pagon RA, Bird TC, Dolan CR, Stephens K. 2000, Seattle, WA: University of Washington, updated 2010"},{"key":"1079_CR10","doi-asserted-by":"publisher","first-page":"e57","DOI":"10.1093\/nar\/gnf056","volume":"30","author":"JP Schouten","year":"2002","unstructured":"Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G: Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res. 2002, 30: e57-10.1093\/nar\/gnf056.","journal-title":"Nucleic Acids Res"},{"key":"1079_CR11","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/nrg2520","volume":"10","author":"JF Bateman","year":"2009","unstructured":"Bateman JF, Boot-Handford RP, Lamande SR: Genetic diseases of connective tissues: cellular and extracellular effects of ECM mutations. 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