{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:20:57Z","timestamp":1790191257802,"version":"4.1.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the National Key R&D Program of China","award":["No. 2018YFC1002404"],"award-info":[{"award-number":["No. 2018YFC1002404"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Pediatr"],"abstract":"<jats:sec>\n                <jats:title>Abstract<\/jats:title>\n                <jats:p>Patients with Aarskog\u2013Scott syndrome (AAS) have short stature, facial anomalies, skeletal deformities, and genitourinary malformations. FYVE, RhoGEF, and PH domain-containing 1 (<jats:italic>FGD1<\/jats:italic>) is the only known causative gene of AAS. However, the diagnosis of AAS remains difficult, and specific treatments are still absent. Patients suspected with AAS were recruited, and clinical information was collected. Genetic testing and functional analysis were carried out for the diagnosis. By literature review, we summarized the clinical and genetic characteristics of <jats:italic>FGD1<\/jats:italic>-related AAS and analyzed the genotype\u2013phenotype correlation. Five patients were recruited, and four novel <jats:italic>FGD1<\/jats:italic> variants were identified. The diagnosis of AAS was confirmed by genetic analysis and functional study. Three patients treated with growth hormone showed improved heights during the follow-up period. By literature review, clinical features of AAS patients with <jats:italic>FGD1<\/jats:italic> variants were summarized. Regarding <jats:italic>FGD1<\/jats:italic> variations, substitutions were the most common form, and among them, missense variants were the most frequent. Moreover, we found patients with drastic variants showed higher incidences of foot and genitourinary malformations. Missense variants in DH domain were related to a lower incidence of cryptorchidism.<\/jats:p>\n                <jats:p>\u00a0 <jats:italic>Conclusion<\/jats:italic>: We reported four novel pathogenic <jats:italic>FGD1<\/jats:italic> variations in AAS patients and confirmed the efficacy and safety of growth hormone treatment in <jats:italic>FGD1<\/jats:italic>-related AAS patients with growth hormone deficiency. Additionally, our literature review suggested the crucial role of DH domain in FGD1 function.\n<jats:table-wrap><jats:table><jats:tbody>\n                      <jats:tr>\n                        <jats:td colspan=\"2\"><jats:bold>What is Known:<\/jats:bold><jats:italic>\u2022 Aarskog\u2013Scott syndrome is a rare genetic disease, and the only known cause is the variant in FGD1 gene. The typical clinical manifestations of AAS include facial, skeletal, and urogenital deformities and short stature.<\/jats:italic><\/jats:td>\n                      <\/jats:tr>\n                      <jats:tr>\n                        <jats:td colspan=\"2\"><jats:bold>What is New:<\/jats:bold><jats:italic>\u2022 We reported four novel FGD1 variants and reported the treatment of growth hormone in FGD1-related AAS patients. Our genotype\u2013phenotype correlation analysis suggested the crucial role of DH domain in FGD1 function.<\/jats:italic><\/jats:td>\n                      <\/jats:tr>\n                    <\/jats:tbody><\/jats:table><\/jats:table-wrap><\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00431-024-05484-9","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T13:02:24Z","timestamp":1709038944000},"page":"2257-2272","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["FGD1-related Aarskog\u2013Scott syndrome: Identification of four novel variations and a literature review of clinical and molecular aspects"],"prefix":"10.1007","volume":"183","author":[{"given":"Sujuan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anran","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"issue":"5","key":"5484_CR1","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1016\/S0022-3476(70)80247-5","volume":"77","author":"D Aarskog","year":"1970","unstructured":"Aarskog D (1970) A familial syndrome of short stature associated with facial dysplasia and genital anomalies. 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The human study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-IRB20180703).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written informed consents were obtained from the parents.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Subjects or their legal representatives participating in this study provided written consent for publication of the results.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}