Pulmonary fibrosis in non‐mutation carriers of families with short telomere syndrome gene mutations

Respirology ◽  
2021 ◽  
Author(s):  
Joanne J. Vis ◽  
Jasper J. Smagt ◽  
Aernoud A. Batenburg ◽  
Roel Goldschmeding ◽  
H. Wouter Es ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Gene Mutations ◽  
Short Telomere ◽  
Mutation Carriers

Pulmonary fibrosis in non-mutation carriers of families with short telomere syndrome gene mutations

2021 ◽  
Author(s):  
Annette J. van der Vis ◽  
Jasper Van Der Smagt ◽  
Aernoud Van Batenburg ◽  
Wouter Van Es ◽  
Jan Grutters ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Gene Mutations ◽  
Short Telomere ◽  
Mutation Carriers

scholarly journals Cancer spectrum and outcomes in the Mendelian short telomere syndromes

Blood ◽  
2020 ◽  
Vol 135 (22) ◽  
pp. 1946-1956 ◽  
Author(s):  
Kristen E. Schratz ◽  
Lisa Haley ◽  
Sonye K. Danoff ◽  
Amanda L. Blackford ◽  
Amy E. DeZern ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Young Male ◽  
Hepatopulmonary Syndrome ◽  
Telomere Maintenance ◽  
Short Telomere ◽  
Inherited Disorders ◽  
Monosomy 7 ◽  
Clonal Hematopoiesis ◽  
Mutation Carriers ◽  
Age Related

Abstract Short telomeres have been linked to cancer risk, yet other evidence supports them being tumor suppressive. Here, we report cancer outcomes in individuals with germline mutations in telomerase and other telomere-maintenance genes. Among 180 individuals evaluated in a hospital-based setting, 12.8% had cancer. Solid tumors were rare (2.8%); nearly all were young male DKC1 mutation carriers, and they were generally resectable with good short-term outcomes. Myelodysplastic syndrome (MDS) was most common, followed by acute myeloid leukemia (AML); they accounted for 75% of cancers. Age over 50 years was the biggest risk factor, and MDS/AML usually manifested with marrow hypoplasia and monosomy 7, but the somatic mutation landscape was indistinct from unselected patients. One- and 2-year survival were 61% and 39%, respectively, and two-thirds of MDS/AML patients died of pulmonary fibrosis and/or hepatopulmonary syndrome. In one-half of the cases, MDS/AML patients showed a recurrent peripheral blood pattern of acquired, granulocyte-specific telomere shortening. This attrition was absent in age-matched mutation carriers who did not have MDS/AML. We tested whether adult short telomere patients without MDS/AML also had evidence of clonal hematopoiesis of indeterminate potential–related mutations and found that 30% were affected. These patients also primarily suffered morbidity from pulmonary fibrosis during follow-up. Our data show that the Mendelian short telomere syndromes are associated with a relatively narrow cancer spectrum, primarily MDS and AML. They suggest that short telomere length is sufficient to drive premature age-related clonal hematopoiesis in these inherited disorders.

Detection of mitochondrial transfer RNA (mt-tRNA) gene mutations in patients with idiopathic pulmonary fibrosis and sarcoidosis

Mitochondrion ◽  
2018 ◽  
Vol 43 ◽  
pp. 43-52 ◽  
Author(s):  
Zoe Daniil ◽  
Ourania S. Kotsiou ◽  
Alexandros Grammatikopoulos ◽  
Sotiria Peletidou ◽  
Helen Gkika ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Trna Gene ◽  
Gene Mutations ◽  
Transfer Rna ◽  
Mitochondrial Transfer

scholarly journals BMPR2 mutation status influences bronchial vascular changes in pulmonary arterial hypertension

2016 ◽  
Vol 48 (6) ◽  
pp. 1668-1681 ◽  
Author(s):  
Maria-Rosa Ghigna ◽  
Christophe Guignabert ◽  
David Montani ◽  
Barbara Girerd ◽  
Xavier Jaïs ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Bronchial Artery ◽  
Gene Mutations ◽  
Systemic Circulation ◽  
Systematic Analysis ◽  
Mutation Status ◽  
Mutation Carriers ◽  
Pulmonary Arterial ◽  
The Impact

The impact of bone morphogenetic protein receptor 2 (BMPR2) gene mutations on vascular remodelling in pulmonary arterial hypertension (PAH) is unknown. We sought to identify a histological profile of BMPR2 mutation carriers.Clinical data and lung histology from 44 PAH patients were subjected to systematic analysis and morphometry.Bronchial artery hypertrophy/dilatation and bronchial angiogenesis, as well as muscular remodelling of septal veins were significantly increased in PAH lungs carrying BMPR2 mutations. We found that patients displaying increased bronchial artery remodelling and bronchial microvessel density, irrespective of the mutation status, were more likely to suffer from severe haemoptysis. History of substantial haemoptysis (>50 mL) was significantly more frequent in BMPR2 mutation carriers. 43.5% of BMPR2 mutation carriers, as opposed to 9.5% of noncarriers, displayed singular large fibrovascular lesions, which appear to be closely related to the systemic lung vasculature.Our analysis provides evidence for the involvement of the pulmonary systemic circulation in BMPR2 mutation-related PAH. We show that BMPR2 mutation carriers are more prone to haemoptysis and that haemoptysis is closely correlated to bronchial arterial remodelling and angiogenesis; in turn, pronounced changes in the systemic vasculature correlate with increased pulmonary venous remodelling, creating a distinctive profile in PAH patients harbouring a BMPR2 mutation.

Clinical Charactistics of Ph-Negative MPN Patients with Coexistence of JAK2V617F, Calr and MPL Mutation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Dan Ma ◽  
Ping Liu ◽  
Chengyun Pan ◽  
Bingqing Cheng ◽  
Yaming Zhang ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Conflicts Of Interest ◽  
Gene Mutations ◽  
Interferon Α ◽  
Driver Gene ◽  
Fisher Exact Test ◽  
Single Mutation ◽  
Double Mutation ◽  
Mutation Carriers ◽  
Pubmed Database

Background and purpose: JAK2, CALR and MPL gene mutations are the driver genes leading to the pathogenesis of ph-negative myeloproliferative meoplasm (MPN). However, it's still unkonwn about the effect of double gene mutations coexisting in ph-negative MPN patients. In this study, we analyzed the clinical significance of the three driver gene mutations when they coexisted in patients with MPN. Methods: Collected bone marrow or peripheral blood samples of 221 patients with suspected MPN who were in the Affiliated Hospital of Guizhou Medical University between May 2017 and April 2020; qPCR detection for JAK2V617F mutation and sanger sequencing detection for CALR gene exon 9 and MPL Exon 10 mutation. Searched Pubmed database related to the coexistence of the three driver gene mutations and extracted information; Fisher exact test to analyze the differences in clinical characteristics between double mutation carriers and single mutation carriers. Shapiro-Wilk statistical analysis of the differences in clinical characteristics of ET patients with different types of double mutations. Results: 1 ET and 1 PMF patient carried both JAK2V617F and CALR gene mutations were found in our center, accounting for 0.9% of ph-negative MPN. The CALR carried by PMF patients was a newly discovered mutation type, c.1126_1127insTTTGC, R376Lfs*56. Through database search, we collected 26 literatures involving MPN case reports with double-driver gene mutations. By fitting analysis with the clinical information of positive patients in our center, a total of 74 MPN patients were collected, of which the number of ET patients was the largest(57/74, accounting for 77.03%). The most common coexisting mutant type was JAK2V617F plus CALR (63/74, 85.14%). The age of onset of MPN patients with double-driver gene mutations was significantly higher than that of single-mutation carriers, and the proportion of patients over 70 years of age was higher (p<0.05), and double mutation carriers had higher platelet count levels(Plt) (p<0.05). The proportion of patients with splenomegalia was lower (p<0.05). The clinical characteristics of ET patients were similar to MPN patients, but no difference in the incidence of splenomegalia (p>0.05). Among PMF patients, the Plt and the proportion of patients with megasplenomegaly in double mutation carriers were similar to those in MPN patients, but the hemoglobin(Hb) was higher (p<0.05). In addition, we also compared the clinical characteristics of ET patients with different gene mutation types. The results showed that the Hb of patients with JAK2V617F and CALR mutations were higher than those of ET patients with JAK2V617F and MPL mutations (p<0.05), but the Plt level is low (p<0.05). Although there were no significant differences in age, gender, IPSET-thrombosis and IPSET (IWG-MRT) scores and WBC between the two groups, the proportion of female ET patients with JAKV617F with MPL mutation was significantly higher than that of JAK2V617F with CALR mutation group (p<0.05). And the proportion of patients with WBC exceeding 11×109/L was also higher (p<0.05). In addition, only one PV patient carried JAK2V617F and CALR, and achieved partial or complete remission after treatment with standard treatment regimens (hydroxyurea or interferon-α). Conclusion: JAK2V617F, CALR and MPL gene mutations are not mutually exclusive in MPN patients, but a certain number of double mutation carriers are ignored. Compared with patients with single-gene mutations, patients with double-gene mutations are older and have higher platelet counts, and should be treated differently in later treatment. At the same time, there are also differences between ET patients with different mutation combinations. These results suggest that it is very necessary for MPN patients to check for three driver gene mutations at the same time, and this type of patients may become a new subtype of MPN. Disclosures No relevant conflicts of interest to declare.

scholarly journals Lung transplantation in telomerase mutation carriers with pulmonary fibrosis

2014 ◽  
Vol 44 (1) ◽  
pp. 178-187 ◽  
Author(s):  
L. L. Silhan ◽  
P. D. Shah ◽  
D. C. Chambers ◽  
L. D. Snyder ◽  
G. C. Riise ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Transplantation ◽  
Mutation Carriers

M1933 A Comprehensive Analysis of the Phenotypic Manifestations of Mismatch Repair Gene Mutations: Comparing MSH6 with MLH1 and MSH2 Mutation Carriers

2009 ◽  
Vol 136 (5) ◽  
pp. A-449-A-450
Author(s):  
Fay Kastrinos ◽  
Ewout W Steyerberg ◽  
Judith Balmaña ◽  
Sapna Syngal
Keyword(s):  
Mismatch Repair ◽  
Gene Mutations ◽  
Comprehensive Analysis ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Msh2 Mutation ◽  
Mutation Carriers ◽  
Mismatch Repair Gene Mutations

scholarly journals Short telomere length and its correlation with gene mutations in myelodysplastic syndrome

2016 ◽  
Vol 9 (1) ◽  
Author(s):  
Sang Mee Hwang ◽  
Seon Young Kim ◽  
Jung Ah Kim ◽  
Hee-Sue Park ◽  
Si Nae Park ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Telomere Length ◽  
Gene Mutations ◽  
Short Telomere

Malignant Head and Neck Paragangliomas in SDHB Mutation Carriers

2007 ◽  
Vol 137 (1) ◽  
pp. 126-129 ◽  
Author(s):  
Carsten Christof Boedeker ◽  
Hartmut P. H. Neumann ◽  
Wolfgang Maier ◽  
Birke Bausch ◽  
Jörg Schipper ◽  
...  
Keyword(s):  
Head And Neck ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Distant Metastases ◽  
High Rate ◽  
Body Region ◽  
Sdhb Mutation ◽  
Sdhd Gene ◽  
Mutation Carriers ◽  
Head And Neck Paragangliomas

OBJECTIVE: Three of four paraganglioma syndromes (PGLs) have been characterized on a molecular genetic basis. PGL 1 is associated with mutations of the succinate dehydrogenase subunit D ( SDHD) gene, PGL 3 is caused by SDHC gene mutations, and PGL 4 is caused by SDHB gene mutations. The objective of this study was to investigate whether PGLs are associated with malignant head and neck paragangliomas (HNPs). STUDY DESIGN AND SETTING: Through November 2005, we screened 195 HNP patients for mutations of the genes SDHB, SDHC, and SDHD. RESULTS: We detected 5 SDHC, 13 SDHB, and 45 SDHD gene mutations. In seven SDHB mutation carriers, there were distant metastases. No signs of metastases were found in SDHC and SDHD patients. One patient with a sporadic HNP presented with locally metastatic disease. CONCLUSIONS: SDHB mutations are associated with a high rate of malignant HNPs. SIGNIFICANCE: In SDHB patients, a three-body region imaging and scintigraphy or DOPA-PET must be performed to exclude metastases.

scholarly journals CADM1 and SPC25 gene mutations in lung cancer patients with idiopathic pulmonary fibrosis

2021 ◽  
pp. 100232
Author(s):  
Aya Fukuizumi ◽  
Rintaro Noro ◽  
Masahiro Seike ◽  
Akihiko Miyanaga ◽  
Yuji Minegishi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cancer Patients ◽  
Gene Mutations ◽  
Lung Cancer Patients
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