{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T09:16:07Z","timestamp":1771492567483,"version":"3.50.1"},"reference-count":12,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":42,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Skeletal dysplasias are a common cause of short stature and are often linked with multisystemic features. The Hedgehog signaling pathway plays a vital role in skeletal development and is regulated by the protein kinase domain-containing cytoplasmic (PKDCC) gene, also known as vertebrate lonesome kinase. Pathogenic variants in the PKDCC gene have been reported in very few patients worldwide and are inherited in an autosomal recessive pattern. We report 2 siblings\u2014a 6-year-old girl and a 3-year-old boy\u2014who present with rhizomelic short stature, facial dysmorphism, low-set ears, and umbilical hernia. The girl has a history of cardiac septal defects and camptodactyly, while her younger brother shows no systemic complications. A comprehensive laboratory panel was normal in both siblings, and whole exome sequencing revealed a homozygous splice acceptor variant of the PKDCC gene on chromosome 2:g.42280377A&amp;gt;T, (NM_138370.3, c.640-2A&amp;gt;T), leading to a diagnosis of rhizomelic limb shortening with dysmorphic features. To our knowledge, this is the first report of siblings from India with a PKDCC pathogenic variant, underscoring the importance of genetic screening in cases of short stature accompanied by dysmorphism and dysplasia.<\/jats:p>","DOI":"10.1210\/jcemcr\/luag010","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T12:43:30Z","timestamp":1768394610000},"source":"Crossref","is-referenced-by-count":0,"title":["Rhizomelic short stature with dysmorphism in two siblings due to\n                    <i>PKDCC<\/i>\n                    gene pathogenic variants"],"prefix":"10.1210","volume":"4","author":[{"given":"Arun","family":"Guddeti","sequence":"first","affiliation":[{"name":"Department of Endocrinology, ESIC Medical College and Hospital , Hyderabad 500038 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anushri","family":"Sridharan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, ESIC Medical College and Hospital , Hyderabad 500038 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, ESIC Medical College and Hospital , Hyderabad 500038 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V","family":"Sai Ramya","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, ESIC Medical College and Hospital , Hyderabad 500038 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayyad","family":"Aleem","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, ESIC Medical College and Hospital , Hyderabad 500038 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9601-0320","authenticated-orcid":false,"given":"K V S","family":"Hari Kumar","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, ESIC Medical College and Hospital , Hyderabad 500038 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"2026021903261718100_luag010-B1","doi-asserted-by":"crossref","first-page":"1229666","DOI":"10.3389\/fped.2023.1229666","article-title":"What the pediatric endocrinologist needs to know about skeletal dysplasia, a primer","volume":"11","author":"Legare","year":"2023","journal-title":"Front Pediatr"},{"issue":"12","key":"2026021903261718100_luag010-B2","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1002\/ajmg.a.61366","article-title":"Nosology and classification of genetic skeletal disorders: 2019 revision","volume":"179","author":"Mortier","year":"2019","journal-title":"Am J Med Genet A"},{"issue":"9","key":"2026021903261718100_luag010-B3","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/nrrheum.2015.84","article-title":"The role of Hedgehog signalling in skeletal health and disease","volume":"11","author":"Alman","year":"2015","journal-title":"Nat Rev Rheumatol"},{"issue":"1","key":"2026021903261718100_luag010-B4","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1042\/BCJ20190784","article-title":"Secreted tyrosine kinase Vlk negatively regulates Hedgehog signaling by inducing lysosomal degradation of smoothened","volume":"477","author":"Kim","year":"2020","journal-title":"Biochem J"},{"issue":"12","key":"2026021903261718100_luag010-B5","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1136\/jmedgenet-2018-105639","article-title":"Biallelic disruption of PKDCC is associated with a skeletal disorder characterised by rhizomelic shortening of extremities and dysmorphic features","volume":"56","author":"Sajan","year":"2019","journal-title":"J Med Genet"},{"issue":"1","key":"2026021903261718100_luag010-B6","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/cge.14324","article-title":"The prevalence and phenotypic range associated with biallelic PKDCC variants","volume":"104","author":"Pagnamenta","year":"2023","journal-title":"Clin Genet"},{"issue":"12","key":"2026021903261718100_luag010-B7","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1242\/dev.026435","article-title":"The novel protein kinase Vlk is essential for stromal function of mesenchymal cells","volume":"136","author":"Kinoshita","year":"2009","journal-title":"Development"},{"issue":"1","key":"2026021903261718100_luag010-B8","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/dvdy.21822","article-title":"Short limbs, cleft palate, and delayed formation of flat proliferative chondrocytes in mice with targeted disruption of a putative protein kinase gene, Pkdcc (AW548124)","volume":"238","author":"Imuta","year":"2009","journal-title":"Dev Dyn"},{"issue":"4-5","key":"2026021903261718100_luag010-B9","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.diff.2013.03.002","article-title":"The Hedgehog target Vlk genetically interacts with Gli3 to regulate chondrocyte differentiation during mouse long bone development","volume":"85","author":"Probst","year":"2013","journal-title":"Differentiation"},{"issue":"1","key":"2026021903261718100_luag010-B10","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1186\/s12920-023-01631-7","article-title":"Prenatal diagnosis to identify compound heterozygous variants in PKDCC that causes rhizomelic limb shortening with dysmorphic features in a fetus from China","volume":"16","author":"Yan","year":"2023","journal-title":"BMC Med Genomics"},{"issue":"6","key":"2026021903261718100_luag010-B11","doi-asserted-by":"crossref","first-page":"e2477","DOI":"10.1002\/mgg3.2477","article-title":"Prenatal diagnosis of a skeletal disorder characterized by rhizomelic shortening of limbs caused by compound heterozygous variants in the PKDCC gene: case report and literature review","volume":"12","author":"Wang","year":"2024","journal-title":"Mol Genet Genomic Med"},{"issue":"20","key":"2026021903261718100_luag010-B12","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1056\/NEJMoa2035790","article-title":"100,000 genomes pilot on rare-disease diagnosis in health care - preliminary report","volume":"385","author":"GPP Investigators","year":"2021","journal-title":"N Engl J Med"}],"container-title":["JCEM Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/4\/2\/luag010\/66988332\/luag010.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/4\/2\/luag010\/66988332\/luag010.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T08:26:27Z","timestamp":1771489587000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcemcr\/article\/doi\/10.1210\/jcemcr\/luag010\/8490169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,8]]},"references-count":12,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,1,8]]}},"URL":"https:\/\/doi.org\/10.1210\/jcemcr\/luag010","relation":{},"ISSN":["2755-1520"],"issn-type":[{"value":"2755-1520","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,2]]},"published":{"date-parts":[[2026,1,8]]},"article-number":"luag010"}}