{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T06:12:01Z","timestamp":1771481521806,"version":"3.50.1"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"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":"\n Background<\/jats:title>\n Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia-1 (EDM1) are two rare skeletal diseases that represent distinct endpoints of a continuous phenotypic spectrum with substantial clinical overlap, caused by variants in the gene coding cartilage oligomeric matrix protein (COMP).<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n \n To summarize the clinical characteristics of PSACH\/EDM1 and variants of\n COMP<\/jats:italic>\n gene, as well as to explore the correlations between them.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n PubMed, China National Knowledge Infrastructure, and Wanfang were searched for case reports and case series of patients with genetic diagnosis of PSACH\/EDM1 from the inception to 24 March 2025. The clinical characteristics and gene variants of enrolled patients were analyzed and compared to explore genotype-phenotype correlation.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 830 PSACH\/EDM1 patients (471probands) harboring 224 different variants of\n COMP<\/jats:italic>\n gene were enrolled from 106 articles, with missense variants accounting for the majority (80.8%). Exon 13 (183 probands, 38.9%) and type III (T3) repeat domain (413 probands, 87.7%) were the most commonly affected regions, with c.1417_1419del (p.Asp473del) being the most common hotspot variant. Compared with EDM1, PSACH manifested earlier age of onset (\n p<\/jats:italic>\n &lt; 0.001), shorter stature (\n p<\/jats:italic>\n &lt; 0.001), higher rates of lower limb deformity (\n p<\/jats:italic>\n &lt; 0.001), joint laxity (\n p<\/jats:italic>\n = 0.041), anterior beaking of the vertebra and irregular\/flared metaphysis (\n p<\/jats:italic>\n &lt; 0.001), while lower rate of joint pain\/osteoarthritis (\n p<\/jats:italic>\n &lt; 0.001) and abnormal femoral head (\n p<\/jats:italic>\n = 0.008). Missense variants in T3\u20134 and T3\u20135 were more likely to cause EDM1 (all\n p<\/jats:italic>\n &lt; 0.001), while those in T3\u20131 and T3\u20136 to T3\u20138 were associated with a greater frequency of PSACH (\n p<\/jats:italic>\n = 0.002 to 0.023). Majority of in-frame variants were found in PSACH, as c.1417_1419del (p.Asp473del) being PSACH specific.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n PSACH exhibits more severe phenotypes than EDM1, even with phenotypic overlap. In-frame variants are more strongly associated with PSACH, as the hotspot variant p.Asp473del exclusively identified in PSACH. In contrast, missense variants in T3\u20134 and T3\u20135 show a stronger association with EDM1.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fendo.2026.1740770","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T05:23:07Z","timestamp":1771478587000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genotype-phenotype correlations in PSACH\/EDM1 patients with COMP gene variants: a comprehensive review of 830 cases"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaolin","family":"Ni","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Genetics and Metabolism, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liya","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics and Metabolism, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weibo","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics and Metabolism, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0795-330","article-title":"Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene","volume":"10","author":"Briggs","year":"1995","journal-title":"Nat Genet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0795-325","article-title":"Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia","volume":"10","author":"Hecht","year":"1995","journal-title":"Nat Genet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3642","DOI":"10.1038\/s41467-020-17378-z","article-title":"Mutations in COMP cause familial carpal tunnel syndrome","volume":"11","author":"Li","year":"2020","journal-title":"Nat Commun"},{"key":"B4","article-title":"COMP-related 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