{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:28:32Z","timestamp":1782865712936,"version":"3.54.5"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pycnodysostosis (PD, OMIM # 265800) is a rare variant of skeletal dysplasia with an autosomal recessive type of inheritance, characterized by a combination of specific features such as disproportionate nanism, generalized osteosclerosis, and distinct craniofacial dysmorphism. Radiographic features include acro\u2010osteolysis of the distal phalanges in association with sclerosing bone lesions with multiple fractures. The polymorphism of the clinical manifestations of pycnodysostosis and low prevalence of the disorder lead to the difficulties with early.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The following tests were used for diagnostics: genealogical analysis, clinical examination, neurological examination according to the standard method with an assessment of the psychoemotional sphere, radiological analysis, searching for pathogenic variants in the <jats:italic>CTSK<\/jats:italic> gene by the automated Sanger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We describe first clinical and genetic characteristics of three Russian patients with pycnodysostosis from unrelated families. Two patients have a novel homozygous nucleotide substitution c.746T&gt;A (p. Ile249Asn), and one has a previously described homozygous pathogenic variant c.746T&gt;C (p.Ile249Thr) in the <jats:italic>CTSK<\/jats:italic> gene. In all three cases, a transition or transversion was found at nucleotide position 746 in exon 6 of the <jats:italic>CTSK<\/jats:italic> gene, leading to two different amino acid substitutions in the polypeptide chain. The obtained results may indicate the presence of a major pathogenic variant in the <jats:italic>CTSK<\/jats:italic> gene, leading to the typical manifestation of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The data presented in the study enlarge the clinical, radiological, and mutational spectrum of pycnodysostosis. Typical clinical manifestations and the small size of the <jats:italic>CTSK<\/jats:italic> gene make the automated Sanger sequencing the optimal method for diagnosis of pycnodysostosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1904","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T03:29:53Z","timestamp":1647919793000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Clinical and genetic characterization of three Russian patients with pycnodysostosis due to pathogenic variants in the CTSK gene"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2672-6294","authenticated-orcid":false,"given":"Tatiana Vladimirovna","family":"Markova","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Kenis","sequence":"additional","affiliation":[{"name":"H.Turner National Medical Research Center for \u0421hildren's Orthopedics and Trauma Surgery  Pushkin Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeniy","family":"Melchenko","sequence":"additional","affiliation":[{"name":"H.Turner National Medical Research Center for \u0421hildren's Orthopedics and Trauma Surgery  Pushkin Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darya","family":"Guseva","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5863-3543","authenticated-orcid":false,"given":"Darya","family":"Osipova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nailya","family":"Galeeva","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Nagornova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Leonidovna","family":"Dadali","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"issue":"3","key":"e_1_2_9_2_1","first-page":"492","article-title":"Clinical and radiographic maxillofacial features of pycnodysostosis","volume":"7","author":"Alves N.","year":"2014","journal-title":"International Journal of Clinical and Experimental Medicine"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-016-0228-7"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-9-60"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13591"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9490"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/bmme.1996.0088"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5279.1236"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0695-235"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-015-9963-y"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1148\/rg.317115093"},{"issue":"70","key":"e_1_2_9_12_1","first-page":"999","article-title":"Pycnodysostosis","volume":"25","author":"Maroteaux P.","year":"1962","journal-title":"Presse M\u00e9dicale"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.21.13955"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61366"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0695-238"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.4158\/ACCR-2020-0169"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.1968.02100020072010"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.779"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10212"},{"key":"e_1_2_9_20_1","unstructured":"The WHO Child Growth Standards.XXXXXXn.d.https:\/\/www.who.int\/tools\/child\u2010growth\u2010standards\/standards"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-20"}],"container-title":["Molecular Genetics &amp; 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