{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T14:33:53Z","timestamp":1771511633735,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T00:00:00Z","timestamp":1511222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2015\u201002424"],"award-info":[{"award-number":["2015\u201002424"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007051","name":"Uppsala Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004681","name":"Higher Education Commission, Pakistan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004681","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003748","name":"Svenska S\u00e4llskapet f\u00f6r Medicinsk Forskning","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003748","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2018,1]]},"abstract":"The phenotypic spectrum associated with heterozygous mutations in cartilage oligomeric matrix protein gene (COMP<\/jats:styled-content><\/jats:italic>) range from a mild form of multiple epiphyseal dysplasia (MED<\/jats:styled-content>) to pseudoachondroplasia (PSACH<\/jats:styled-content>). However, the phenotypic effect from biallelic COMP<\/jats:styled-content><\/jats:italic> variants is unclear. We investigated a large consanguineous Pakistani family with a severe form of PSACH<\/jats:styled-content> in 2 individuals. Another 14 family members presented with a mild PSACH<\/jats:styled-content> phenotype similar to MED<\/jats:styled-content>. Using exome sequencing and subsequent segregation analysis, we identified homozygosity for a COMP<\/jats:styled-content><\/jats:italic> missense variant [c.1423G<\/jats:styled-content>>A; p.(D475N<\/jats:styled-content>)] in the 2 severely affected individuals, whereas family members with the mild PSACH<\/jats:styled-content> phenotype were heterozygous. Our observations show for the first time that a biallelic COMP<\/jats:styled-content><\/jats:italic> variant may be associated with pronounced and widespread skeletal malformations suggesting an additive effect of the 2 mutated alleles.<\/jats:p>","DOI":"10.1111\/cge.13091","type":"journal-article","created":{"date-parts":[[2017,7,7]],"date-time":"2017-07-07T13:05:22Z","timestamp":1499432722000},"page":"182-186","source":"Crossref","is-referenced-by-count":7,"title":["Homozygosity for a missense variant in COMP<\/scp><\/i> gene associated with severe pseudoachondroplasia"],"prefix":"10.1111","volume":"93","author":[{"given":"M.","family":"Tariq","sequence":"first","affiliation":[{"name":"Human Molecular Genetics Laboratory, Health Biotechnology Division National Institute for Biotechnology and Genetic Engineering (NIBGE) Faisalabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.N.","family":"Khan","sequence":"additional","affiliation":[{"name":"Human Molecular Genetics Laboratory, Health Biotechnology Division National Institute for Biotechnology and Genetic Engineering (NIBGE) Faisalabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Lundin","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences Uppsala University Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Jameel","sequence":"additional","affiliation":[{"name":"Human Molecular Genetics Laboratory, Health Biotechnology Division National Institute for Biotechnology and Genetic Engineering (NIBGE) Faisalabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"L\u00f6nnerholm","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences Uppsala University Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.M.","family":"Baig","sequence":"additional","affiliation":[{"name":"Human Molecular Genetics Laboratory, Health Biotechnology Division National Institute for Biotechnology and Genetic Engineering (NIBGE) Faisalabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Dahl","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Science for Life Laboratory Uppsala University Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4185-7409","authenticated-orcid":false,"given":"J.","family":"Klar","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Science for Life Laboratory Uppsala University Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,11,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10066"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21611"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19981228)80:5<510::AID-AJMG14>3.0.CO;2-F"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"issue":"4","key":"e_1_2_6_6_1","first-page":"367","article-title":"Growth centile charts (anthropometric measurement) of Pakistani pediatric population","volume":"62","author":"Aziz S","year":"2012","journal-title":"J Pak Med Assoc"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.18003413502"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2007.01.004"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.12.4366-4371.2002"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2520"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-1332"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.12.018"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.12.001"},{"issue":"5","key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1136\/jmg.23.5.425","article-title":"Pseudoachondroplasia: clinical diagnosis at different ages and comparison of autosomal dominant and recessive types. A review of 32 patients (26 kindreds)","volume":"23","author":"Wynne\u2010Davies R","year":"1986","journal-title":"J Med Genet"},{"issue":"2","key":"e_1_2_6_15_1","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1136\/jmg.22.2.150","article-title":"Severe pseudoachondroplasia with parental consanguinity","volume":"22","author":"Young ID","year":"1985","journal-title":"J Med Genet"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01006905"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.13091","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13091","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T01:59:50Z","timestamp":1696039190000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.13091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,21]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.1111\/cge.13091"],"URL":"https:\/\/doi.org\/10.1111\/cge.13091","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,21]]}}}