Whole‐exome sequencing improves genetic testing accuracy in pulmonary artery hypertension

Zeng, Xiaofang; Lian, Tian‐Yu; Lin, Jie; Li, Suqi; Zheng, Hongyu; Chen, Cheng; Ye, Jue; Jing, Zhi‐Cheng; Wang, Xiaojian; Huang, Wei

doi:10.1177/2045894018763682

Cited by 4 publications

(3 citation statements)

References 38 publications

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“…Further, PVOD represents poor prognosis such that the current mean time for diagnosis to death and first symptom to death are 14.3 ± 19.3 and 24.7 ± 24.8 months [15]. Likewise, our patient underwent an aggressive disease phenotype in a shorter timeline that Whole exome sequencing is one of the most prominent next generation sequencing technology, which is widely used in understanding the genetic etiology of a disease; provides an advantage that all genes driving the disease could be investigated in a robust, cheaper and high throughput fashion [20]. With the advancement of technology, the cost of data analysis and interpretation associated with whole exome sequencing has dropped as low as USD 500 per sample; the genetic testing application has rapidly evolved and genetic testing/counseling has been increasing available in many PAH centers [21,22].…”

Section: Discussionmentioning

confidence: 95%

Rapid disease progress in a PVOD patient carrying a novel EIF2AK4 mutation: a case report

et al. 2020

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Background Pulmonary veno-occlusive disease (PVOD) and pulmonary arterial hypertension (PAH) share an overlapping disease phenotype. Hence it is necessary to distinguish them. Case presentation Our 14-year-old female patient admitted with progressive shortness of breath, dizziness, and fatigue even after minimal physical activity was clinically suspected for PAH, based on her previous history. Her chest computed tomography artery reported the presence of PVOD triad features - subpleural thickened septal lines, ground-glass nodules/opacities and mediastinal lymphadenopathy. Because of her weak physical stature, a lung biopsy was not performed; however, the genetic testing identified a novel heterozygous EIF2AK4 mutation at c.4833_4836dup (p.Q1613Kfs*10) - the dominant susceptible factor driving PVOD. Combination of genetic testing and computed tomography artery facilitated us to distinguish PVOD from PAH. Her disease symptoms advanced aggressively so that she died even before the lung transplantation, which was less than 6 months from the onset of disease symptoms. Conclusion This case report highlights that novel EIF2AK4 mutation at [c.4833_4836dup (p.Q1613Kfs*10)] would predict an aggressive phenotype of PVOD. Hence, we conclude that a genetic test identifying EIF2AK4 mutation would serve as a tool for the early diagnosis of PVOD, circumventing lung biopsy.

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Section: Discussionmentioning

confidence: 95%

Rapid disease progress in a PVOD patient carrying a novel EIF2AK4 mutation: a case report

et al. 2020

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“…However, Tenorio et al reported that the EIF2AK4 mutation c.3344C > T (p. P1115 L) caused an early onset of disease and low survival rate in six consanguineous PVOD patients [ 8 ]. Another report of a case of an EIF2AK4 mutation at c.4833_4836dup (p. Q1613Kfs*10), reported that this mutation caused an aggressive phenotype, such that the time from onset of disease symptoms to death was less than 6 months [ 28 ]. We are surprised to note that all of those patients who responded well to PAH-targeted therapies had the EIF2AK4 mutation located in the degenerate kinase-like domain (amino acids between 280 and 537), while the aggressive phenotype mutation is located at the HisRS domain (amino acids between 1021 and 1492) or C-terminal (amino acids between 1492 and 1648) [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Pulmonary veno-occlusive disease in Sjogren's syndrome: a case report

Zeng

Liu²,

Rathinasabapathy³

et al. 2023

BMC Pulm Med

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Background Pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD) belongs to Group 1 pulmonary hypertension. Pulmonary veno-occlusive disease (PVOD), which is characterized by venous system aberrations, has been previously reported in CTD-PAH; however, it has rarely been observed in Sjogren’s syndrome (SS). Case presentation Our 28-year-old female patient was admitted to the hospital with recurrent shortness of breath even after minimal physical activity. Her chest high-resolution CT scan demonstrated pulmonary artery dilatation and bilateral ground-glass nodules. A subsequent right heart catheterization confirmed pulmonary hypertension because her mean pulmonary arterial pressure was 62 mmHg. Our inquisitive genomic assessment identified a novel EIF2AK4 mutation at c.1021 C > T (p. Gln341*), the dominant causal gene of PVOD. Histological examination demonstrated stenosis and occlusions in the pulmonary veins. Because she presented with features such as dry eyes and Raynaud's phenomenon, we performed a biopsy on the labial salivary gland, which confirmed SS. Her treatment regimen included PAH-targeted therapies (tadalafil and macitentan) in combination with hydroxychloroquine. Although she was hospitalized several times due to acute exacerbation of PAH, her disease progression was under control, and she did not demonstrate any signs of pulmonary edema even after a three-year treatment period. Conclusion Here, we report the case of an SS-PAH patient with PVOD who carried a novel biallelic EIF2AK4 mutation, and PAH-targeted therapies were well tolerated by our patient.

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“…[20][21][22][23][24][25] In the analyses of practice gaps 5 and 7, additional published data related to methodology dependent FN, false-positive, or true-positive rates were used. 15,20,22,[25][26][27][28][29][30][31][32][33][34][35] Furthermore, in the analyses of practice gaps 5 and 7, additional third-party real-time laboratory data from US-based laboratories were used to supplement the Medicare claims data and laboratory test results data (eg, test performance and positivity rates) included in the Diaceutics repository. A total of 5,589 patients with aNSCLC newly diagnosed in 2019 were identified within the real-time laboratory data set.…”

Section: Data Source and Populationmentioning

confidence: 99%

Impact of Clinical Practice Gaps on the Implementation of Personalized Medicine in Advanced Non–Small-Cell Lung Cancer

Sadik

Pritchard²,

Keeling

et al. 2022

JCO Precision Oncology

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PURPOSE Personalized medicine presents new opportunities for patients with cancer. However, many patients do not receive the most effective personalized treatments because of challenges associated with integrating predictive biomarker testing into clinical care. Patients are lost at various steps along the precision oncology pathway because of operational inefficiencies, limited understanding of biomarker strategies, inappropriate testing result usage, and access barriers. We examine the impact of various clinical practice gaps associated with diagnostic testing-informed personalized medicine strategies on the treatment of advanced non–small-cell lung cancer (aNSCLC). METHODS Using Diaceutics' Data Repository, a multisource database including commercial and Medicare claims and laboratory data from over 500,000 patients with non–small-cell lung cancer in the United States, we analyzed the number of patients with newly diagnosed aNSCLC who could have, but did not, benefit from a personalized treatment. The analysis focuses on the independent and cumulative impacts of gaps occurring during seven steps of the precision oncology pathway, from diagnosis to treatment. RESULTS For every 1,000 patients in the study cohort, 497 (49.7%) are lost to precision oncology because of factors associated with getting biomarker test results. Among the 503 of 1,000 patients who did receive results from a biomarker test, 147 (29.2%) did not receive appropriate targeted treatments. Thus, approximately 64% of potentially eligible patients with aNSCLC are not benefiting from precision oncology therapies appropriate for their disease. CONCLUSION Most patients with aNSCLC eligible for precision oncology treatments do not benefit from them because of clinical practice gaps. This finding is likely reflective of similar gaps in other cancer types. An increased understanding of the impact of each practice gap can inform strategies to improve the delivery of precision oncology, helping to fully realize the promise of personalized medicine.

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Whole‐exome sequencing improves genetic testing accuracy in pulmonary artery hypertension

Cited by 4 publications

References 38 publications

Rapid disease progress in a PVOD patient carrying a novel EIF2AK4 mutation: a case report

Rapid disease progress in a PVOD patient carrying a novel EIF2AK4 mutation: a case report

Pulmonary veno-occlusive disease in Sjogren's syndrome: a case report

Impact of Clinical Practice Gaps on the Implementation of Personalized Medicine in Advanced Non–Small-Cell Lung Cancer

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