{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:37:43Z","timestamp":1790206663913,"version":"4.1.0"},"reference-count":13,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017638","name":"Ministry of Health of the Russian Federation","doi-asserted-by":"publisher","award":["200079056"],"award-info":[{"award-number":["200079056"]}],"id":[{"id":"10.13039\/501100017638","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Background.<\/ns3:bold>\n                    \u00a0This study deals with a rare (orphan) monogenic connective tissue\u00a0disorder - Ehlers-Danlos syndrome\u00a0kyphoscoliotic\u00a0type 2\u00a0(EDSKS2).\u00a0Kyphoscoliotic\u00a0type 2 Ehlers-Danlos syndrome is an autosomal recessive disorder caused by mutations in the\u00a0FKBP14\u00a0gene (7p14.3), which encodes the FKBP22 protein.\u00a0According to the 2017 classification, this type is in group seven - collagen spatial structure and cross-linking defects. We present results of clinical examination and molecular genetic analysis for\u00a0five patients with age varying from two to\u00a0fifteen\u00a0years.\u00a0\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Methods.<\/ns3:bold>\n                    \u00a0Five patients were examined using clinical and laboratory methods.\u00a0DNA samples used for the analysis were extracted from whole blood samples using a Wizard\u00ae\u00a0Genomic DNA Purification Kit (Promega, USA) according to the manufacturer's protocol.\u00a0\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Results.<\/ns3:bold>\n                    \u00a0The major clinical findings were kyphoscoliosis, early motor development delay, muscular weakness, hypotonia and hearing loss. Molecular genetic analysis\u00a0detected a homozygous c.362dupC duplication in exon 3 of the\u00a0FKBP14\u00a0gene in all\u00a0five patients. This mutation is common in various countries. Differential diagnostics were carried out to exclude other Ehlers-Danlos syndrome types and myopathies.\u00a0\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Conclusions.<\/ns3:bold>\n                    \u00a0Literature analysis and examination of five\u00a0EDSKS2\u00a0patients demonstrated the involvement of major organs and systems, such as joints, spine, muscles, cardiovascular system, respiratory system, hearing, and vision, into the pathological process. Kidney mobility increases and\u00a0nephroptosis\u00a0seems to be secondary caused by muscular weakness. During molecular genetic analysis, to verify EDSKS2 it is recommended to initially search for the c.362dupC duplication, which appears to be common in European countries, including Russia.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.52268.1","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T10:00:08Z","timestamp":1624615208000},"page":"502","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Ehlers-Danlos syndrome\u00a0kyphoscoliotic\u00a0type 2 caused by mutations in the\u00a0FKBP14\u00a0gene: an analysis of five cases"],"prefix":"10.12688","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4026-3791","authenticated-orcid":false,"given":"Alla Nikolaevna","family":"Semyachkina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina Alexandrovna","family":"Nikolaeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nailya Mansurovna","family":"Galeeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander Vladimirovich","family":"Polyakov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Andreevna","family":"Kurnikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5930-1965","authenticated-orcid":false,"given":"Vera \u0410lexandrovna","family":"Belova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina Valerievna","family":"Shulyakova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya Sergeevich","family":"Dantsev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goar Vladimirovna","family":"Dzhivanshiryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"8-26","DOI":"10.1002\/ajmg.c.31552","article-title":"The 2017 international classification of the Ehlers-Danlos syndromes.","volume":"175","author":"F Malfait","year":"2017","journal-title":"Am J Med Genet C Semin Med Genet."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/1750-1172-6-46","article-title":"Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA): clinical, molecular and biochemical delineation.","volume":"6","author":"M Rohrbach","year":"2011","journal-title":"Orphanet J Rare 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Genet."},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.4121\/14705859.v1","article-title":"Underlying data for \u2018Ehlers-Danlos syndrome kyphoscoliotic type 2 caused by mutations in the FKBP14 gene: an analysis of five cases.","author":"A Semyachkina","year":"2021","journal-title":"4TU.ResearchData."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"2031-2038","DOI":"10.1002\/ajmg.a.37728","article-title":"Further delineation of FKBP14-related Ehlers-Danlos syndrome: A patient with early vascular complications and non-progressive kyphoscoliosis, and literature review.","volume":"170","author":"C Dordoni","year":"2016","journal-title":"Am J Med Genet A."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"64-67","DOI":"10.1111\/ced.12983","article-title":"Ehlers-Danlos syndrome related to FKBP14 mutations: detailed cutaneous phenotype.","volume":"42","author":"A Bursztejn","year":"2017","journal-title":"Clin Exp Dermatol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"42-54","DOI":"10.1038\/gim.2017.70","article-title":"A cohort of 17 patients with kyphoscoliotic Ehlers\u2013Danlos syndrome caused by biallelic mutations in FKBP14: expansion of the clinical and mutational spectrum and description of the natural history.","volume":"20","author":"C Giunta","year":"2018","journal-title":"Genet Med."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e274-e278","DOI":"10.5546\/aap.2019.eng.e274","article-title":"FKBP14 kyphoscoliotic Ehlers-Danlos Syndrome in adolescent patient: the first Colombian report.","volume":"117","author":"F Ruiz-Botero","year":"2019","journal-title":"Arch Argent Pediatr."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/s41598-019-57374-y","article-title":"The novel missense mutation Met48Lys in FKBP22 changes its structure and functions.","volume":"10","author":"Y Ishikawa","year":"2020","journal-title":"Sci 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.55519.r88243, Matthias Baumann, Division of Pediatric Neurology, Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria, 12 Jul 2021, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/10-502\/v1#referee-response-88243","order":0,"name":"referee-response-88243","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.55519.r90354, Tomoki Kosho, Department of Medical Genetics, Shinshu University School of Medicine, Nagano, Japan, 31 Aug 2021, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/10-502\/v1#referee-response-90354","order":1,"name":"referee-response-90354","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was financially supported by the Government Assignment of the Russian Ministry of Health, Assignment No. 200079056. The funders had no role in the study design; in the collection, analysis, or interpretation of the data; or in the preparation, review, or approval of the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}