{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T22:57:53Z","timestamp":1762642673814,"version":"3.40.5"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21ek0109493","JP21ek0109549","JP21ek0109486","JP20bm0804006","JP20ek0109486"],"award-info":[{"award-number":["JP21ek0109493","JP21ek0109549","JP21ek0109486","JP20bm0804006","JP20ek0109486"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Kyphomelic dysplasia is a heterogeneous group of skeletal dysplasias characterized by severe bowing of the limbs associated with other variable findings, such as narrow thorax and abnormal facies. We searched for the genetic etiology of this disorder. Four individuals diagnosed with kyphomelic dysplasia were enrolled. We performed whole\u2010exome sequencing and evaluated the pathogenicity of the identified variants. All individuals had de novo heterozygous variants in <jats:italic>KIF5B<\/jats:italic> encoding kinesin\u20101 heavy chain: two with c.272A&gt;G:p.(Lys91Arg), one with c.584C&gt;A:p.(Thr195Lys), and the other with c.701G&gt;T:p.(Gly234Val). All variants involved conserved amino acids in or close to the ATPase activity\u2010related motifs in the catalytic motor domain of the KIF5B protein. All individuals had sharp angulation of the femora and humeri, distinctive facial features, and neonatal respiratory distress. Short stature was observed in three individuals. Three developed postnatal osteoporosis with subsequent fractures, two showed brachycephaly, and two were diagnosed with optic atrophy. Our findings suggest that heterozygous <jats:italic>KIF5B<\/jats:italic> deleterious variants cause a specific form of kyphomelic dysplasia. Furthermore, alterations in kinesins cause various symptoms known as kinesinopathies, and our findings also extend the phenotypic spectrum of kinesinopathies.<\/jats:p>","DOI":"10.1111\/cge.14133","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T05:03:11Z","timestamp":1648443791000},"page":"3-11","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["De novo heterozygous variants in <i>KIF5B<\/i> cause kyphomelic dysplasia"],"prefix":"10.1111","volume":"102","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9774-0464","authenticated-orcid":false,"given":"Toshiyuki","family":"Itai","sequence":"first","affiliation":[{"name":"Department of Human Genetics Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2153-1252","authenticated-orcid":false,"given":"Zheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory for Bone and Joint Diseases RIKEN Center for Integrative Medical Sciences  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gen","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Center for Intractable Diseases Saitama Medical University Hospital  Saitama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9898-2230","authenticated-orcid":false,"given":"Hirofumi","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Saitama Children's Medical Center  Saitama 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Medical Center  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5807-2523","authenticated-orcid":false,"given":"Hiroshi","family":"Doi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Medicine Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6817-7748","authenticated-orcid":false,"given":"Kenji","family":"Kurosawa","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4052-5066","authenticated-orcid":false,"given":"Yoshihiro","family":"Hotta","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Hamamatsu University School of Medicine  Hamamatsu 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