Idiopathic pulmonary fibrosis: Epidemiology, natural history and pathophysiology
Muhunthan Thillai, David R Moller, Keith C Meyer in Clinical Handbook of Interstitial Lung Disease, 2017
Clues to the importance of a genetic component in the development of pulmonary fibrosis came from the recognition of familial disease and from specific known genetic disorders including dyskeratosis congenita and Hermansky–Pudlak syndrome. Dyskeratosis congenita is a rare, heritable condition characterized by bone marrow failure and mucocutaneous features, and is commonly complicated by pulmonary fibrosis (63,64). The disease is caused by genetic mutations in genes responsible for telomerase maintenance. This observation led to an examination of telomerase genes in familial forms of lung fibrosis not associated with dyskeratosis congenita. This identified an association between familial pulmonary fibrosis (FPF) and mutations in TERT and TERC (65,66). Similarly, other studies identified variants in genes encoding surfactant protein C (SFTPC), surfactant protein A2 (SFTPA2) (67–69). Together however, these mutations account for only a minority of cases of pulmonary fibrosis.
Haematology
Stephan Strobel, Lewis Spitz, Stephen D. Marks in Great Ormond Street Handbook of Paediatrics, 2019
Clinical manifestations in dyskeratosis congenita (DC) often appear during childhood, although there is a wide age range most likely reflecting the type of mutation causing DC. Skin pigmentation and nail changes (Fig. 11.35) typically appear first with bone marrow failure occuring a number of years later. The clinical complexity of the disease has expanded in recent years to include: idiopathic aplastic anaemia +/– MDS; (ii) idiopathic pulmonary fibrosis; (iii) the Hoyeraal–Hreidarrson syndrome, characterised by microencephaly, cerebellar hypoplasia, growth retardation, enteropathy and immunodeficiency with or without aplastic anaemia; (iv) a presentation overlapping Revesz syndrome or Coats plus, with retinopathy and intracranial calcifications.
Accident and Emergency
Nagi Giumma Barakat in Get Through, 2006
7.D: There are no other features of Fanconi anaemia. C: Pancreatic insufficiency is associated with Shwachman-Diamond syndrome.G: Skin changes with an increased risk of cancer and bone marrow failure are the main characteristic features of dyskeratosis congenita.E: The DNA repair study will be normal, and the presence of the thumb is another feature of TAR syndrome.
Ribosomopathies and cancer: pharmacological implications
Published in Expert Review of Clinical Pharmacology, 2022
Gazmend Temaj, Sarmistha Saha, Shpend Dragusha, Valon Ejupi, Brigitta Buttari, Elisabetta Profumo, Lule Beqa, Luciano Saso
10) Dyskeratosis congenita is a disorder that affects many parts of the body. Three features are characteristic of this disorder: a) fingernails and toenails that grow poorly or are abnormally shaped (nail dystrophy); b) changes in skin coloring (pigmentation), especially on the neck and chest, in a pattern often described as ‘lacy’; and c) white patches inside the mouth. Individuals with congenital dyskeratosis may develop leukemia, pulmonary fibrosis, eye abnormalities, hair loss, low bone mineralization, and dental problems. They have a higher risk of developing cancer in different body parts [277,278]. In patients affected with this type of disease, mutations in TERT, TERC, DKC1, and TINF2 have been found. hTR and hTER are the main telomerase components produced by TERC and TERT genes, respectively. hTR is an RNA molecule, a chimerical cousin of DNA [279–281].
Unilateral Coats’-like disease and an intragenic deletion in the TERC gene: A case report
Published in Ophthalmic Genetics, 2018
G. Peene, E. Smets, E. Legius, C. Cassiman
Dyskeratosis congenita (DC) is an inherited bone marrow failure and cancer susceptibility syndrome caused by germline mutations in telomere biology genes (Ballew and Savage 2013; Dokal et al. 2014). It is clinically diagnosed by the presence of the diagnostic triad of reticular skin pigmentation, nail dysplasia, and oral leukoplakia; however, phenotypic heterogeneity is common. Germline mutations in DKC1 (OMIM 300126), TINF2 (OMIM 604319), TERC (OMIM 602322), TERT (OMIM 187270), NOP10 (OMIM 606471), NHP2 (OMIM 606470), WRAP53 (OMIM 612661), CTC1 (OMIM 613129), RTEL1 (OMIM 608833), ACD (OMIM 609377) (Kocak et al. 2014), and PARN (OMIM 604212) (Dhanraj et al. 2015; Moon et al. 2015) genes account for approximately 70% of classic DC (Dokal et al. 2014; Bertuch 2015).
Severe immunochemotherapy-induced toxicities in a patient with dyskeratosis congenita and literature review
Published in Hematology, 2022
Jiayi Geng, Menglin Zhao, Qiuyu Li
Dyskeratosis congenita (DC) is a rare inheritable disease with an estimated prevalence of 1/100000 in the population and a 13:1 male predominance[1]. DC belongs to a class of diseases referred to as telomere biology disorders (TBDs), in which abnormally short telomere lengths and telomere biological defects act as pathogenic factors [2]. To date, mutations in more than a dozen genes encoding telomere biology proteins have been described to cause TBDs. These mutations can be inherited in an X-linked recessive, autosomal dominant, or autosomal recessive pattern, while de novo and somatic mutations have only rarely been found [1–3].