{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T21:09:27Z","timestamp":1779138567311,"version":"3.51.4"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":41,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,24]]},"abstract":"<jats:p>\n                    Kenny-Caffey syndrome (KCS) is a rare genetic disorder characterized by extreme short stature, cortical thickening and medullary stenosis of tubular bones, facial dysmorphism, abnormal T cell function, and hypoparathyroidism. Biallelic loss-of-function variants in\n                    <jats:italic>TBCE<\/jats:italic>\n                    cause autosomal recessive type 1 KCS (KCS1). By contrast, heterozygous missense variants in a restricted region of the\n                    <jats:italic>FAM111A<\/jats:italic>\n                    gene have been identified in autosomal dominant type 2 KCS (KCS2) and a more severe lethal phenotype, osteocraniostenosis (OCS); these variants have recently been shown to confer a gain of function. In this study, we describe 2 unrelated children with KCS and OCS who were homozygous for different\n                    <jats:italic>FAM111A<\/jats:italic>\n                    variant alleles that result in replacement of the same residue, Tyr414 (c.1241A&gt;G, p.Y414C and c.1240T&gt;A, p.Y414N), in the mature FAM111A protein. Their heterozygous relatives are asymptomatic. Functional studies of recombinant FAM111A\n                    <jats:sup>Y414C<\/jats:sup>\n                    demonstrated normal dimerization and a mild gain-of-function effect. This study provides evidence that both biallelic and monoallelic variants of\n                    <jats:italic>FAM111A<\/jats:italic>\n                    with varying degrees of activation can lead to dominant or recessive KCS2 and OCS.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.186862","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T12:00:21Z","timestamp":1739275221000},"source":"Crossref","is-referenced-by-count":2,"title":["Quantitative hypermorphic FAM111A alleles cause autosomal recessive Kenny-Caffey syndrome type 2 and osteocraniostenosis"],"prefix":"10.1172","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2265-6727","authenticated-orcid":true,"given":"Dong","family":"Li","sequence":"first","affiliation":[{"name":"Center for Applied Genomics, The Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA."},{"name":"Department of Pediatrics, University of Pennsylvania Perelman School of 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