{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T19:35:15Z","timestamp":1782243315183,"version":"3.54.5"},"reference-count":21,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T00:00:00Z","timestamp":1562025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001869","name":"Academia Sinica","doi-asserted-by":"publisher","award":["CDA-105-L01"],"award-info":[{"award-number":["CDA-105-L01"]}],"id":[{"id":"10.13039\/501100001869","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Science and Technology","award":["105-2311-B-001-055-MY3"],"award-info":[{"award-number":["105-2311-B-001-055-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hoyeraal\u2013Hreidarsson syndrome (HHS), caused by several different germline mutations resulting in severe telomeropathy, presents with early-onset growth anomalies and neurologic\/developmental disorders including characteristic cerebellar hypoplasia. Early mortalities may arise from immunodeficiency and bone marrow failure if not successfully salvaged by allogeneic hematopoietic stem cell transplantation (HSCT). Few reports have characterized the persistent somatic progression of HHS after successful HSCT. We present an HHS patient with an X-linked recessive DKC1 c.1058C &gt; T; Ala353Val mutation who successfully underwent unrelated HSCT at 5 years of age. After months of early infections and organ toxicities immediately post-transplant, he had more than two years of excellent quality of life with correction of bone marrow failure and immunodeficiency. However, episodic massive variceal bleeding and progressive respiratory insufficiency, which were secondary to non-cirrhotic portal hypertension and pulmonary arteriovenous shunts, respectively, developed over 2 years after HSCT and resulted in his death from respiratory failure 4 years after HSCT. This outcome suggests that while HSCT can correct bone marrow failure and immunodeficiency, it may fail to prevent or even aggravate other fatal processes, such as portal hypertension and pulmonary arteriovenous shunting.<\/jats:p>","DOI":"10.3390\/ijms20133261","type":"journal-article","created":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T12:11:17Z","timestamp":1562069477000},"page":"3261","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Complications for a Hoyeraal\u2013Hreidarsson Syndrome Patient with a Germline DKC1 A353V Variant Undergoing Unrelated Peripheral Blood Stem Cell Transplantation"],"prefix":"10.3390","volume":"20","author":[{"given":"Rong-Long","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei 11259, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuanyin K","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9857-068X","authenticated-orcid":false,"given":"Liuh-Yow","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,2]]},"reference":[{"key":"ref_1","unstructured":"(2015). Hreidarsson syndrome, a complex telomere biology disorder. Br. J. Haematol., 170, 457\u2013471."},{"key":"ref_2","doi-asserted-by":"crossref","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":"ref_3","doi-asserted-by":"crossref","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":"ref_4","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/bmt.2008.163","article-title":"Unrelated cord blood transplantation in a girl with Hoyeraal-Hreidarsson syndrome","volume":"42","author":"Coman","year":"2008","journal-title":"Bone Marrow Transpl."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3586","DOI":"10.1182\/blood-2012-08-447755","article-title":"A homozygous telomerase T-motif variant resulting in markedly reduced repeat addition processivity in siblings with Hoyeraal-Hreidarsson syndrome","volume":"121","author":"Gramatges","year":"2013","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/bmt.2015.352","article-title":"TCR-\u03b1\u03b2 and CD19-depleted haploidentical stem cell transplant with reduced intensity conditioning for Hoyeraal\u2013Hreidarsson syndrome with RTEL1 mutation","volume":"51","author":"Bhattacharyya","year":"2016","journal-title":"Bone Marrow Transpl."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1002\/pbc.26030","article-title":"Novel compound heterozygous RTEL1 gene mutations in a patient with Hoyeraal-Hreidarsson syndrome","volume":"63","author":"Moriya","year":"2016","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2941","DOI":"10.1182\/blood.V124.21.2941.2941","article-title":"Full donor myeloid engraftment with minimal toxicity in dyskeratosis congenita patients undergoing allogeneic bone marrow transplantation without radiation or alkylating agents","volume":"124","author":"Lehmann","year":"2014","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/pbc.22061","article-title":"Dyskeratosis congenita: The first NIH clinical research workshop","volume":"53","author":"Savage","year":"2009","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1038\/bmt.2013.35","article-title":"Reduced intensity conditioning is effective for hematopoietic SCT in dyskeratosis congenita-related BM failure","volume":"48","author":"Ayas","year":"2013","journal-title":"Bone Marrow Transpl."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/j.bbmt.2013.05.021","article-title":"Outcomes of allogeneic hematopoietic cell transplantation in patients with dyskeratosis congenita","volume":"19","author":"Gadalla","year":"2013","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/bjh.15495","article-title":"Outcome of haematopoietic stem cell transplantation in dyskeratosis congenita","volume":"183","author":"Fioredda","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/bmt.2010.65","article-title":"Disease-specific hematopoietic cell transplantation: Nonmyeloablative conditioning regimen for dyskeratosis congenita","volume":"46","author":"Dietz","year":"2011","journal-title":"Bone Marrow Transpl."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/acel.12041","article-title":"The gastrointestinal manifestations of telomere-mediated disease","volume":"12","author":"Jonassaint","year":"2013","journal-title":"Aging Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1002\/hep.24173","article-title":"Constitutional telomerase mutations are genetic risk factors for cirrhosis","volume":"53","author":"Calado","year":"2011","journal-title":"Hepatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1002\/hep.24217","article-title":"Telomerase gene mutations are associated with cirrhosis formation","volume":"53","author":"Hartmann","year":"2011","journal-title":"Hepatology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1056\/NEJMoa066157","article-title":"Telomerase mutations in families with idiopathic pulmonary fibrosis","volume":"356","author":"Armanios","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1056\/NEJMra0707185","article-title":"Hepatopulmonary syndrome\u2014A liver-induced lung vascular disorder","volume":"358","author":"Krowka","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1601640","DOI":"10.1183\/13993003.01640-2016","article-title":"Pulmonary arteriovenous malformations: An uncharacterized phenotype of Dyskeratosis Congenita and related Telomere Biology Disorders","volume":"49","author":"Khincha","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1101\/gad.222893.113","article-title":"Molecular basis of telomere syndrome caused by CTC1 mutations","volume":"27","author":"Chen","year":"2013","journal-title":"Genes Dev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1378\/chest.118.3.615","article-title":"Hepatopulmonary syndrome: A prospective study of relationships between severity of liver disease, PaO2 response to 100% oxygen, and brain uptake after 99mTc MAA lung scanning","volume":"118","author":"Krowka","year":"2000","journal-title":"Chest"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/13\/3261\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:01:56Z","timestamp":1760187716000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/13\/3261"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,2]]},"references-count":21,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2019,7]]}},"alternative-id":["ijms20133261"],"URL":"https:\/\/doi.org\/10.3390\/ijms20133261","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,2]]}}}