{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:07:41Z","timestamp":1784696861682,"version":"3.55.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Acromelic dysplasias, including acromicric dysplasia (AD) and geleophysic dysplasia type 2 (GD2), are ultrarare disorders caused by\n                      <jats:italic>FBN1<\/jats:italic>\n                      variants in the transforming growth factor-\u03b2-binding protein-like domain 5 (TB5). These conditions are characterized by severe short stature and variable multisystem involvement, but genotype\u2013phenotype correlations and treatment responses remain incompletely defined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To characterize the clinical spectrum, genotype\u2013phenotype correlations, and growth outcomes in a Chinese cohort of patients with\n                      <jats:italic>FBN1<\/jats:italic>\n                      -related AD\/GD2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective analysis of 14 patients with AD or GD2 from eight unrelated families. Clinical, radiographic, and genetic data were collected. Genotype\u2013phenotype correlations were further explored by integrating data from two previously published cohorts (n = 52). Growth outcomes were evaluated in patients receiving recombinant human growth hormone (rhGH) therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All patients exhibited severe short stature (mean height-SDS of -5.28 \u00b1 1.13) with brachydactyly and delayed bone age. Multisystem involvement, including skeletal abnormalities, airway and otologic complications, skin thickening, joint limitation, hepatomegaly, and cardiopulmonary disease (50.0%, exclusively on GD2), was common. All the variants were heterozygous missense mutations clustered in the TB5 domain, including two novel\n                      <jats:italic>de novo<\/jats:italic>\n                      variants. Genotype\u2013phenotype preliminary analysis revealed a greater mortality in patients with GD2 than in patients with AD (29.6%(15.9 -48.5%) vs. 4.0%(0.7-19.5%), P\u00a0=\u00a00.038). Variants with cysteine or aromatic residues substitutions were associated with increased mortality compared with that associated with other substitutions (overall\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). Eleven patients received growth-promoting therapy. Among the eight patients treated at our center, growth-promoting therapy maintained a growth velocity during the first two years (approximately 6 cm\/year) but declined thereafter, with no significant improvement in height-SDS over a mean treatment duration of 3.6 years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>FBN1<\/jats:italic>\n                      -related AD\/GD2 represent multisystem disorders rather than isolated skeletal dysplasias. Variants affecting cysteine or aromatic residues in the TB5 domain maybe associated with worse outcomes. Growth-promoting therapy may contribute to maintaince of growth velocity but catch-up growth was not clearly observed. These findings suggest that molecular stratification may be helpful for risk assessment and clinical decision-making, pending further validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1883383","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:49:08Z","timestamp":1784695748000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["FBN1 TB5 domain variants in acromelic dysplasia: multisystem manifestations, genotype\u2013phenotype correlations, and partial responses to growth hormone therapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Jun","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University","place":["Guangzhou, 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru-Jiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huang-Meng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua-Mei","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu-Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/352337a0","article-title":"Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene","volume":"352","author":"Dietz","year":"1991","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.ajhg.2011.05.012","article-title":"Mutations in 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