{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T05:57:07Z","timestamp":1768543027235,"version":"3.49.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000},"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. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Dyskeratosis congenita (DC) is a rare inheritable disorder characterized by bone marrow failure and mucocutaneous triad (reticular skin pigmentation, nail dystrophy, and oral leukoplakia). Dyskeratosis congenita 1 (<jats:italic>DKC1<\/jats:italic>) is responsible for 4.6% of the DC with an X-linked inheritance pattern. Almost 70 <jats:italic>DKC1<\/jats:italic> variations causing DC have been reported in the Human Gene Mutation Database.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here we described a 14-year-old boy in a Chinese family with a phenotype of abnormal skin pigmentation on the neck, oral leukoplakia, and nail dysplasia in his hands and feet. Genetic analysis and sequencing revealed hemizygosity for a recurrent missense mutation c.1156G &amp;gt; A (p.Ala386Thr) in <jats:italic>DKC1<\/jats:italic> gene. The heterozygous mutation (c.1156G &amp;gt; A) from his mother and wild-type sequence from his father were obtained in the same site of <jats:italic>DKC1<\/jats:italic>. This mutation was determined as disease causing based on <jats:italic>silico<\/jats:italic> software, but the pathological phenotypes of the proband were milder than previously reported at this position (HGMDCM060959). Homology modeling revealed that the altered amino acid was located near the PUA domain, which might affect the affinity for RNA binding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This <jats:italic>DKC1<\/jats:italic> mutation (c.1156G &amp;gt; A, p.Ala386Thr) was first reported in a Chinese family with mucocutaneous triad phenotype. Our study reveals the pathogenesis of <jats:italic>DKC1<\/jats:italic> c.1156G &amp;gt; A mutation to DC with a benign phenotype, which expands the disease variation database, the understanding of genotype\u2013phenotype correlations, and facilitates the clinical diagnosis of DC in China.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2022.834268","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T05:26:33Z","timestamp":1649222793000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Case Report: A Missense Mutation in Dyskeratosis Congenita 1 Leads to a Benign Form of Dyskeratosis Congenita Syndrome With the Mucocutaneous Triad"],"prefix":"10.3389","volume":"10","author":[{"given":"Liqing","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianwei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuhong","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-An","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changxin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1002\/humu.22397","article-title":"Telomere phenotypes in females with heterozygous mutations in the dyskeratosis congenita 1 (DKC1) gene.","volume":"34","author":"Alder","year":"2013","journal-title":"Hum Mutat."},{"key":"B2","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1111\/ddg.14268","article-title":"Dyskeratosis congenita: a literature review.","volume":"18","author":"AlSabbagh","year":"2020","journal-title":"J Dtsch Dermatol Ges."},{"key":"B3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/s12881-018-0584-y","article-title":"Dyskeratosis congenita with a novel genetic variant in the DKC1 gene: a case report.","volume":"19","author":"Ratnasamy","year":"2018","journal-title":"BMC Med Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2680","DOI":"10.1182\/blood-2005-07-2622","article-title":"Mutations in dyskeratosis congenita: their impact on telomere length and the diversity of clinical presentation.","volume":"107","author":"Vulliamy","year":"2006","journal-title":"Blood."},{"key":"B5","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1128\/mcb.19.1.567","article-title":"A box H\/ACA small nucleolar RNA-like domain at the human telomerase RNA 3\u2019 end.","volume":"19","author":"Mitchell","year":"1999","journal-title":"Mol Cell Biol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1021\/pr500956k","article-title":"Novel insights into the evolution and structural characterization of dyskerin using comprehensive bioinformatics analysis.","volume":"14","author":"Cerrudo","year":"2015","journal-title":"J Proteome Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"426","DOI":"10.4103\/ijd.IJD_716_18","article-title":"Dyskeratosis congenita with DKC1 mutation: a case report.","volume":"65","author":"Zhao","year":"2020","journal-title":"Indian J Dermatol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1136\/thorax.56.11.891","article-title":"X-linked dyskeratosis congenita: restrictive pulmonary disease and a novel mutation.","volume":"56","author":"Safa","year":"2001","journal-title":"Thorax."},{"key":"B9","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1111\/j.1365-2141.2005.05473.x","article-title":"Identification of DKC1 gene mutations in Japanese patients with X-linked dyskeratosis congenita.","volume":"129","author":"Kanegane","year":"2005","journal-title":"Br J Haematol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1007\/s00439-004-1178-7","article-title":"Telomerase RNA deficiency in peripheral blood mononuclear cells in X-linked dyskeratosis congenita.","volume":"115","author":"Wong","year":"2004","journal-title":"Hum Genet."},{"key":"B11","first-page":"581","article-title":"Skewed X-chromosome inactivation in female carriers of dyskeratosis congenita.","volume":"60","author":"Devriendt","year":"1997","journal-title":"Am J Hum Genet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e24383","DOI":"10.1371\/journal.pone.0024383","article-title":"Differences in disease severity but similar telomere lengths in genetic subgroups of patients with telomerase and shelterin mutations.","volume":"6","author":"Vulliamy","year":"2011","journal-title":"PLoS One."},{"key":"B13","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1086\/302446","article-title":"X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene.","volume":"65","author":"Knight","year":"1999","journal-title":"Am J Hum Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1007\/bf00290963","article-title":"Assignment of the gene for dyskeratosis congenita to Xq28.","volume":"72","author":"Connor","year":"1986","journal-title":"Hum Genet."},{"key":"B15","first-page":"129","article-title":"One novel and two recurrent missense DKC1 mutations in patients with dyskeratosis congenita (DKC).","volume":"12","author":"Heiss","year":"2001","journal-title":"Genet Couns."},{"key":"B16","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1046\/j.1365-2141.1999.01690.x","article-title":"Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia (Hoyeraal-Hreidarsson syndrome) due to mutations in the dyskeratosis congenita gene, DKC1.","volume":"107","author":"Knight","year":"1999","journal-title":"Br J Haematol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1002\/ajh.24545","article-title":"Investigation of chromosome X inactivation and clinical phenotypes in female carriers of DKC1 mutations.","volume":"91","author":"Xu","year":"2016","journal-title":"Am J Hematol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1002\/pbc.21733","article-title":"Identification of a novel mutation in DKC1 in dyskeratosis congenita.","volume":"52","author":"Kurnikova","year":"2009","journal-title":"Pediatr Blood Cancer."},{"key":"B19","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.humpath.2014.10.003","article-title":"Pulmonary fibrosis in dyskeratosis congenita: report of 2 cases.","volume":"46","author":"Dvorak","year":"2015","journal-title":"Hum Pathol."},{"key":"B20","first-page":"221","article-title":"A novel missense mutation of DKC1 in dyskeratosis congenita with pulmonary fibrosis.","volume":"30","author":"Hisata","year":"2013","journal-title":"Sarcoidosis Vasc Diffuse Lung Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.bcmd.2012.05.008","article-title":"High resolution melting analysis for the identification of novel mutations in DKC1 and TERT genes in patients with dyskeratosis congenita.","volume":"49","author":"Carrillo","year":"2012","journal-title":"Blood Cells Mol Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1016\/j.celrep.2013.04.030","article-title":"H\/ACA small RNA dysfunctions in disease reveal key roles for noncoding RNA modifications in hematopoietic stem cell differentiation.","volume":"3","author":"Bellodi","year":"2013","journal-title":"Cell Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1002\/pbc.21203","article-title":"X-linked dyskeratosis congenita in Malaysia.","volume":"50","author":"Hamidah","year":"2008","journal-title":"Pediatr Blood Cancer."},{"key":"B24","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s004390100494","article-title":"Identification of novel DKC1 mutations in patients with dyskeratosis congenita: implications for pathophysiology and diagnosis.","volume":"108","author":"Knight","year":"2001","journal-title":"Hum Genet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1182\/blood-2008-07-166421","article-title":"TERC and TERT gene mutations in patients with bone marrow failure and the significance of telomere length measurements.","volume":"113","author":"Du","year":"2009","journal-title":"Blood."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.1016\/j.chest.2020.07.025","article-title":"Synonymous mutation in DKC1 causes telomerase RNA insufficiency manifesting as familial pulmonary fibrosis.","volume":"158","author":"Gaysinskaya","year":"2020","journal-title":"Chest."},{"key":"B27","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.bcmd.2009.10.005","article-title":"Novel mutations of the DKC1 gene in individuals affected with dyskeratosis congenita.","volume":"44","author":"Rostamiani","year":"2010","journal-title":"Blood Cells Mol Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"216","DOI":"10.3760\/cma.j.issn.0253-2727.2016.03.008","article-title":"Clinical and genetic features of dyskeratosis congenital with bone marrow failure in eight patients.","volume":"37","author":"Wan","year":"2016","journal-title":"Zhonghua Xue Ye Xue Za Zhi."},{"key":"B29","first-page":"Ecr11","article-title":"Missense mutation in a patient with X-linked dyskeratosis congenita.","volume":"88","author":"Kraemer","year":"2003","journal-title":"Haematologica."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e23375","DOI":"10.1002\/jcla.23375","article-title":"CD8(+) T-cell senescence and skewed lymphocyte subsets in young dyskeratosis congenita patients with PARN and DKC1 mutations.","volume":"34","author":"Zeng","year":"2020","journal-title":"J Clin Lab Anal."},{"key":"B31","doi-asserted-by":"publisher","first-page":"101540","DOI":"10.1016\/j.scr.2019.101540","article-title":"Telomere dynamics and hematopoietic differentiation of human DKC1-mutant induced pluripotent stem cells.","volume":"40","author":"Donaires","year":"2019","journal-title":"Stem Cell Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1007\/s12098-009-0300-1","article-title":"Identification of DKC1 gene mutation in an Indian patient.","volume":"77","author":"Tamhankar","year":"2010","journal-title":"Indian J Pediatr."},{"key":"B33","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1111\/j.1525-1470.2010.01299.x","article-title":"Dyskeratosis congenita\u2013two siblings with a new missense mutation in the DKC1 gene.","volume":"28","author":"Coelho","year":"2011","journal-title":"Pediatr Dermatol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1055\/s-0036-1578799","article-title":"Novel mutation in the DKC1 gene: neonatal Hoyeraal-Hreidarsson syndrome as a rare differential diagnosis in pontocerebellar hypoplasia, primary microcephaly, and progressive bone marrow failure.","volume":"47","author":"Dehmel","year":"2016","journal-title":"Neuropediatrics."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1111\/ijd.14424","article-title":"A novel DKC1 gene mutation c.1177 A>T (p.I393F) in a case of dyskeratosis congenita with severe telomere shortening.","volume":"58","author":"Mohanty","year":"2019","journal-title":"Int J Dermatol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1007\/s12185-015-1861-6","article-title":"Clinical and genetic features of dyskeratosis congenita, cryptic dyskeratosis congenita, and Hoyeraal-Hreidarsson syndrome in Japan.","volume":"102","author":"Yamaguchi","year":"2015","journal-title":"Int J Hematol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/ng0598-32","article-title":"X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions.","volume":"19","author":"Heiss","year":"1998","journal-title":"Nat Genet."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1378\/chest.13-2224","article-title":"A novel dyskerin (DKC1) mutation is associated with familial interstitial pneumonia.","volume":"146","author":"Kropski","year":"2014","journal-title":"Chest."},{"key":"B39","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1111\/j.0022-202X.2004.23228.x","article-title":"Identification of a novel mutation and a de novo mutation in DKC1 in two Chinese pedigrees with dyskeratosis congenita.","volume":"123","author":"Ding","year":"2004","journal-title":"J Invest Dermatol."},{"key":"B40","first-page":"553","article-title":"Clinical features and genotype analysis in a case of dyskeratosis congenita.","volume":"35","author":"Yuan","year":"2015","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao."},{"key":"B41","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.1002\/ajmg.a.32412","article-title":"An intronic mutation in DKC1 in an infant with H\u00f8yeraal-Hreidarsson syndrome.","author":"Pearson","year":"2008","journal-title":"Am J Med Genet A."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e13695","DOI":"10.1111\/petr.13695","article-title":"Successful liver transplantation in short telomere syndromes without bone marrow failure due to DKC1 mutation.","volume":"24","author":"Del Br\u00edo Castillo","year":"2020","journal-title":"Pediatr Transplant."},{"key":"B43","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.clim.2015.05.020","article-title":"Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders.","volume":"160","author":"van Schouwenburg","year":"2015","journal-title":"Clin Immunol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1136\/jmg.2011.089821","article-title":"Genetic analysis of inherited bone marrow failure syndromes from one prospective, comprehensive and population-based cohort and identification of novel mutations.","volume":"48","author":"Tsangaris","year":"2011","journal-title":"J Med Genet."},{"key":"B45","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.jaci.2016.05.042","article-title":"Primary immunodeficiency diseases: genomic approaches delineate heterogeneous mendelian disorders.","volume":"139","author":"Stray-Pedersen","year":"2017","journal-title":"J Allergy Clin Immunol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"6026","DOI":"10.1158\/0008-5472.can-09-4730","article-title":"Loss of function of the tumor suppressor DKC1 perturbs p27 translation control and contributes to pituitary tumorigenesis.","volume":"70","author":"Bellodi","year":"2010","journal-title":"Cancer Res."}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2022.834268\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T05:26:41Z","timestamp":1649222801000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2022.834268\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,6]]},"references-count":46,"alternative-id":["10.3389\/fped.2022.834268"],"URL":"https:\/\/doi.org\/10.3389\/fped.2022.834268","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,6]]},"article-number":"834268"}}