{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:45:26Z","timestamp":1786117526261,"version":"build-2736575974"},"reference-count":15,"publisher":"Walter de Gruyter GmbH","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,24]]},"abstract":"Abstract<\/jats:title>\n \n Objectives<\/jats:title>\n \n Meier\u2013Gorlin syndrome (MGORS) is a rare primordial dwarfism characterized by microtia, patellar hypoplasia\/aplasia, and short stature. Additional features may include skeletal, respiratory, urogenital, and endocrine abnormalities. 13 genes have been implicated, with\n DONSON<\/jats:italic>\n , essential for replication fork stability and intra\u2013S phase checkpoint activation, being the most recently identified. Only six patients with\n DONSON<\/jats:italic>\n -related MGORS have been reported. This study expands the phenotype by presenting long-term follow-up and prenatal data in two affected siblings.\n <\/jats:p>\n <\/jats:sec>\n \n Case presentation<\/jats:title>\n \n The index patient, a 10-year-old male, had short stature, microcephaly, microtia, craniofacial features, hearing loss, patellar aplasia, and genitourinary anomalies. Despite an early growth delay, his height progressively improved without intervention. Whole-exome sequencing revealed a homozygous pathogenic c.631C>T p.(Arg211Cys) variant in\n DONSON<\/jats:italic>\n (NM_017613.3). Following genetic counseling, the family declined prenatal testing in a subsequent pregnancy complicated by intrauterine growth restriction. The newborn female sibling carried the same variant and displayed\n DONSON<\/jats:italic>\n -related MGORS features, including the first reported case of thumb aplasia. Additional findings in the family included renal hypoplasia, 2\u20134 toe syndactyly, and hypospadias.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n This is the third report of\n DONSON<\/jats:italic>\n c.631C>T p.(Arg211Cys) in Turkish patients. While the recurrence in the same population suggests a founder effect, haplotype\u2013based analysis is required. Thumb aplasia expands the known phenotype of\n DONSON<\/jats:italic>\n -related MGORS, and the observed moderate course of growth retardation offers prognostic value. These findings highlight the importance of including\n DONSON<\/jats:italic>\n in MGORS gene panels, considering population-specific variants, and systematically documenting rare phenotypic features to improve diagnosis, follow-up, and genetic counseling.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1515\/jpem-2025-0470","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T07:58:14Z","timestamp":1769759894000},"page":"388-395","source":"Crossref","is-referenced-by-count":0,"title":["Meier\u2013Gorlin syndrome due to a recurrent\n DONSON<\/i>\n variant in a Turkish family: first report of thumb aplasia and long-term growth data"],"prefix":"10.1515","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3886-3808","authenticated-orcid":false,"given":"Abdullah","family":"Sezer","sequence":"first","affiliation":[{"name":"Department of Medical Genetics , Ankara Etlik City Hospital , Ankara , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2228-6874","authenticated-orcid":false,"given":"Fatma Zehra","family":"Yal\u00e7\u0131n","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics , Ankara Etlik City Hospital , Ankara , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9316-9910","authenticated-orcid":false,"given":"Abdulkerim","family":"Kolk\u0131ran","sequence":"additional","affiliation":[{"name":"Department of Pediatric Genetics , Ankara Etlik City Hospital , Ankara , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3974-2872","authenticated-orcid":false,"given":"Semra","family":"\u00c7etinkaya","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology , Ankara Etlik City Hospital , Ankara , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"2026080613594066438_j_jpem-2025-0470_ref_001","doi-asserted-by":"crossref","unstructured":"de Munnik, SA, Hoefsloot, EH, Roukema, J, Schoots, J, Knoers, NV, Brunner, HG, et al.. Meier-Gorlin syndrome. Orphanet J Rare Dis 2015;10:114. https:\/\/doi.org\/10.1186\/s13023-015-0322-x.","DOI":"10.1186\/s13023-015-0322-x"},{"key":"2026080613594066438_j_jpem-2025-0470_ref_002","doi-asserted-by":"crossref","unstructured":"de Munnik, SA, Bicknell, LS, Aftimos, S, Al-Aama, JY, van Bever, Y, Bober, MB, et al.. Meier\u2013Gorlin syndrome genotype\u2013phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis. Eur J Hum Genet 2012;20:598\u2013606. https:\/\/doi.org\/10.1038\/ejhg.2011.269.","DOI":"10.1038\/ejhg.2011.269"},{"key":"2026080613594066438_j_jpem-2025-0470_ref_003","doi-asserted-by":"crossref","unstructured":"Nielsen-Dandoroff, E, Ruegg, MSG, Bicknell, LS. The expanding genetic and clinical landscape associated with Meier-Gorlin syndrome. Eur J Hum Genet 2023;31:859\u201368. https:\/\/doi.org\/10.1038\/s41431-023-01359-z.","DOI":"10.1038\/s41431-023-01359-z"},{"key":"2026080613594066438_j_jpem-2025-0470_ref_004","doi-asserted-by":"crossref","unstructured":"Reynolds, JJ, Bicknell, LS, Carroll, P, Higgs, MR, Shaheen, R, Murray, JE, et al.. Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism. Nat Genet 2017;49:537\u201349. https:\/\/doi.org\/10.1038\/ng.3790.","DOI":"10.1038\/ng.3790"},{"key":"2026080613594066438_j_jpem-2025-0470_ref_005","doi-asserted-by":"crossref","unstructured":"Bellelli, R, Boulton, SJ. Spotlight on the replisome: aetiology of DNA replication-associated genetic diseases. Trends Genet 2021;37:317\u201336. https:\/\/doi.org\/10.1016\/j.tig.2020.09.008.","DOI":"10.1016\/j.tig.2020.09.008"},{"key":"2026080613594066438_j_jpem-2025-0470_ref_006","doi-asserted-by":"crossref","unstructured":"Schmit, M, Bielinsky, AK. Congenital diseases of DNA replication: clinical phenotypes and molecular mechanisms. Int J Mol Sci 2021;22:911. https:\/\/doi.org\/10.3390\/ijms22020911.","DOI":"10.3390\/ijms22020911"},{"key":"2026080613594066438_j_jpem-2025-0470_ref_007","doi-asserted-by":"crossref","unstructured":"Kingsley, G, Skagia, A, Passaretti, P, Fernandez-Cuesta, C, Reynolds-Winczura, A, Koscielniak, K, et al.. DONSON facilitates Cdc45 and GINS chromatin association and is essential for DNA replication initiation. Nucleic Acids Res 2023;51:9748\u201363. https:\/\/doi.org\/10.1093\/nar\/gkad694.","DOI":"10.1093\/nar\/gkad694"},{"key":"2026080613594066438_j_jpem-2025-0470_ref_008","doi-asserted-by":"crossref","unstructured":"Evrin, C, Alvarez, V, Ainsworth, J, Fujisawa, R, Alabert, C, Labib, KP. DONSON is required for CMG helicase assembly in the mammalian cell cycle. EMBO Rep 2023;24:e57677. https:\/\/doi.org\/10.15252\/embr.202357677.","DOI":"10.15252\/embr.202357677"},{"key":"2026080613594066438_j_jpem-2025-0470_ref_009","doi-asserted-by":"crossref","unstructured":"Cvetkovic, MA, Passaretti, P, Butryn, A, Reynolds-Winczura, A, Kingsley, G, Skagia, A, et al.. The structural mechanism of dimeric DONSON in replicative helicase activation. Mol Cell 2023;83:4017\u201331.e9. https:\/\/doi.org\/10.1016\/j.molcel.2023.09.029.","DOI":"10.1016\/j.molcel.2023.09.029"},{"key":"2026080613594066438_j_jpem-2025-0470_ref_010","doi-asserted-by":"crossref","unstructured":"Neyzi, O, Bundak, R, G\u00f6k\u00e7ay, G, G\u00fcn\u00f6z, H, Furman, A, Darendeliler, F, et al.. Reference values for weight, height, head circumference, and body mass index in Turkish children. J\u00a0Clin Res Pediatr Endocrinol 2015;7:280\u201393. https:\/\/doi.org\/10.4274\/jcrpe.2183.","DOI":"10.4274\/jcrpe.2183"},{"key":"2026080613594066438_j_jpem-2025-0470_ref_011","doi-asserted-by":"crossref","unstructured":"Demir, K, \u00d6zen, S, Konak\u00e7\u0131, E, Ayd\u0131n, M, Darendeliler, F. A comprehensive online calculator for pediatric endocrinologists: \u00c7EDD \u00c7\u00f6z\u00fcm\/TPEDS metrics. J\u00a0Clin Res Pediatr Endocrinol 2017;9:182\u20134. https:\/\/doi.org\/10.4274\/jcrpe.4526.","DOI":"10.4274\/jcrpe.4526"},{"key":"2026080613594066438_j_jpem-2025-0470_ref_012","doi-asserted-by":"crossref","unstructured":"Karaca, E, Posey, JE, Bostwick, B, Liu, P, Gezdirici, A, Yesil, G, et al.. Biallelic and De Novo variants in DONSON reveal a clinical spectrum of cell cycle\u2010opathies with microcephaly, Dwarfism and Skeletal abnormalities. Am J Med Genet 2019;179:2056\u201366. https:\/\/doi.org\/10.1002\/ajmg.a.61315.","DOI":"10.1002\/ajmg.a.61315"},{"key":"2026080613594066438_j_jpem-2025-0470_ref_013","doi-asserted-by":"crossref","unstructured":"Knapp, KM, Sullivan, R, Murray, J, Gimenez, G, Arn, P, D\u2019Souza, P, et al.. Linked-read genome sequencing identifies biallelic pathogenic variants in DONSON as a novel cause of Meier-Gorlin syndrome. J\u00a0Med Genet 2020;57:195\u2013202. https:\/\/doi.org\/10.1136\/jmedgenet-2019-106396.","DOI":"10.1136\/jmedgenet-2019-106396"},{"key":"2026080613594066438_j_jpem-2025-0470_ref_014","doi-asserted-by":"crossref","unstructured":"Nerakh, G, Vineeth, VS, Tallapaka, K, Nair, L, Dalal, A, Aggarwal, S. Microcephalic primordial dwarfism with predominant Meier\u2013Gorlin phenotype, ichthyosis, and multiple joint deformities\u2014Further expansion of DONSON cell cycle\u2010opathy phenotypic spectrum. Am J Med Genet 2022;188:2139\u201346. https:\/\/doi.org\/10.1002\/ajmg.a.62725.","DOI":"10.1002\/ajmg.a.62725"},{"key":"2026080613594066438_j_jpem-2025-0470_ref_015","doi-asserted-by":"crossref","unstructured":"Li, X, Zhang, LZ, Yu, L, Long, ZL, Lin, AY, Gou, CY. Prenatal diagnosis of Meier-Gorlin syndrome 7: a case presentation. 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