{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T05:27:07Z","timestamp":1767850027191,"version":"3.49.0"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004047","name":"Karolinska Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Musculoskelet Disord"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Skeletal dysplasia is a heterogeneous group of disorders resulting from different genetic variants in humans. The current study was designed to identify the genetic causes of skeletal dysplasia and short stature in two consanguineous families from Pakistan, both comprised of multiple affected individuals. Patients in one family had proportionate short stature with reduced head circumference while affected individuals in the other family had disproportionate short stature.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Clinical data were obtained and radiological examinations of the index patients were completed. Whole genome sequencing for probands from both families were performed followed by Sanger sequencing to confirm segregation of identified variants in the respective families. In-silico pathogenicity score prediction for identified variant and amino acid conservation analysis was completed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Whole Genome Sequencing identified a known biallelic variant c.6176_6189delGTCAGCTGCCGAAG; p.(Gln2060ArgfsTer48) in <jats:italic>PCNT<\/jats:italic> gene and a novel biallelic variant c.174delC; p.(Asp60ThrfsTer7) in <jats:italic>RAB33B<\/jats:italic> gene respectively in affected members of the two families. Clinical imaging revealed platyspondyly and varus deformity in the legs of the affected members in the first family. Radiographs indicated severe platyspondyly, genu valgus deformity of legs and pectus carinatum for the patients in the second family.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>In this study we report the phenotypes and genetic variants in two unrelated families with two distinct forms of skeletal dysplasia. This study strengthens the previous findings that patients harboring <jats:italic>PCNT<\/jats:italic> variants are phenotypically homogeneous and also extends the genotypic spectrum of <jats:italic>RAB33B<\/jats:italic> variants.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12891-021-04503-2","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T20:02:43Z","timestamp":1626811363000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["RAB33B and PCNT variants in two Pakistani families with skeletal dysplasia and short stature"],"prefix":"10.1186","volume":"22","author":[{"given":"Noor ul","family":"Ain","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zunaira","family":"Fatima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadaf","family":"Naz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Outi","family":"Makitie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"issue":"12","key":"4503_CR1","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1136\/jmg.2009.067298","volume":"47","author":"M Willems","year":"2010","unstructured":"Willems M, Genevieve D, Borck G, Baumann C, Baujat G, Bieth E, et al. 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Written informed consents were obtained from the participants and parents for their minor children. All procedures were performed in accordance with relevant guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from patients and parents of minors for publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"630"}}