Clinical Manifestations of Egfr Gene Mutations in Patients with Adenocarcinoma of the Lung Among Inhabitants of the South Russian Region

Abstract Background Dyschromatosis universalis hereditaria (DUH) is a pigmentary dermatosis characterized by generalized mottled macules with hypopigmention and hyperpigmention. ABCB6 and SASH1 are recently reported pathogenic genes related to DUH, and the aim of this study was to identify the causative mutations in a Chinese family with DUH. Methods Sanger sequencing was performed to investigate the clinical manifestation and molecular genetic basis of these familial cases of DUH, bioinformatics tools and multiple sequence alignment were used to analyse the pathogenicity of mutations. Results A novel missense mutation, c.1529G>A, in the SASH1 gene was identified, and this mutation was not found in the National Center for Biotechnology Information Database of Short Genetic Variation, Online Mendelian Inheritance in Man, ClinVar, or 1000 Genomes Project databases. All in silico predictors suggested that the observed substitution mutation was deleterious. Furthermore, multiple sequence alignment of SASH1 revealed that the p.S510N mutation was highly conserved during evolution. In addition, we reviewed the previously reported DUH-related gene mutations in SASH1 and ABCB6. Conclusion Although the affected family members had identical mutations, differences in the clinical manifestations of these family members were observed, which reveals the complexity of the phenotype-influencing factors in DUH. Our findings reveal the mutation responsible for DUH in this family and broaden the mutational spectrum of the SASH1 gene.

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Prevalence and clinical phenotype of the triplicated α-globin genes and its ethnic and geographical distribution in Guizhou of China

BMC Medical Genomics ◽

10.1186/s12920-021-00944-9 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Xi Luo ◽

Xiang-mei Zhang ◽

Liu-song Wu ◽

Jindong Chen ◽

Yan Chen

Keyword(s):

Genetic Counseling ◽

Peripheral Blood ◽

Clinical Phenotype ◽

Globin Gene ◽

Clinical Manifestations ◽

Gene Mutations ◽

Guizhou Province ◽

Globin Genes ◽

Phenotype Correlation ◽

Chi Square

Abstract Background α-thalassemia is relatively endemic in Guizhou province of southwestern China. To predict the clinical manifestations of α-globin gene aberration for genetic counseling, we examined the prevalence of the α-globin triplication and the genotype–phenotype correlation in this subpopulation Methods A cohort of 7644 subjects was selected from nine ethnicities covering four regions in Guizhou province of China. Peripheral blood was collected from each participant for routine blood testing and hemoglobin electrophoresis. PCR-DNA sequencing and Gap-PCR were used to identify the thalassemia gene mutations. Chi-square tests and one-way analysis of variance (ANOVA) were used to statistically analyze the data. Results We found that the frequency of α-globin triplication in Guizhou province was 0.772% (59/7644). Genotypically, the αααanti4.2/αα accounted for 0.523% (40/7644), the αααanti3.7/αα for 0.235% (18/7644), and the αααanti3.7/–SEA for 0.013% (1/7644). The αααanti4.2/αα is more prevalent than the αααanti3.7/αα in Guizhou. In addition, the frequency of the HKαα/αα (that by GAP-PCR is like αααanti4.2/-α3.7) was 0.235% (18/7644). Ethnically, the Tujia group presented the highest prevalence (2.47%) of α-globin triplication. Geographically, the highest frequency of the α-globin triplication was identified in Qiannan region (2.23%). Of the triplicated α-globin cases, 5 coinherited with heterozygote β-thalassemia and presented various clinical manifestations of anemia. Conclusions These data will be used to update the Chinese triplicated α-globin thalassemia database and provide insights into the pathogenesis of thalassemia. These findings will be helpful for the diagnosis of thalassemia and future genetic counseling in those regions.

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EGFR Gene Mutations: A Call for Global x Global Views of Cancer

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/dji079 ◽

2005 ◽

Vol 97 (5) ◽

pp. 326-328 ◽

Cited By ~ 17

Author(s):

W. R. Sellers ◽

M. Meyerson

Keyword(s):

Gene Mutations ◽

Egfr Gene

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Clinical manifestations of familial exudative vitreoretinopathy in children with nucleotide sequence alterations in the FZD4 gene

Russian Ophthalmological Journal ◽

10.21516/2072-0076-2021-14-4-52-59 ◽

2021 ◽

Vol 14 (4) ◽

pp. 52-59

Author(s):

L. A. Katargina ◽

V. V. Kadyshev ◽

E. V. Denisova ◽

E. A. Geraskina ◽

A. V. Marakhonov ◽

...

Keyword(s):

Nucleotide Sequence ◽

Direct Sequencing ◽

Molecular Genetic ◽

Clinical Manifestations ◽

Gene Mutations ◽

Interdisciplinary Approach ◽

Ophthalmological Examination ◽

Photographic Recording ◽

Familial Exudative Vitreoretinopathy ◽

National Medical

Familial exudative vitreoretinopathy (FEVR)is a rare genetically heterogeneous disease with multiple types of inheritance (autosomal dominant, autosomal recessive, X-linked) and widely varying clinical features. Up to 40 % of cases of FEVR are associated with mutations of the FZD4 gene.Purpose: to investigate the clinical manifestations of FEVR in children with nucleotide sequence alterations in the FZD4 gene. Material and methods. The Helmholtz National Medical ResearchCenter of Eye Diseases and the ResearchCentre for MedicalGenetics conducted a joint in-depth ophthalmological examination of 18 patients aged from 3 weeks to 17 years with a diagnosis of FEVR, which included a detailed ophthalmoscopy under drug mydriasis, ultrasound and electrophysiological examination, photographic recording of fundus changes using RetCam and Fundus Foto. Molecular genetic examination was carried out by direct sequencing according to Sanger. Results. Nucleotide sequence alterations in the FZD4 gene were detected in 3 patients(16.7 %)from two unrelated families. In one family, a 12-year-old girl wasfound to display the firstsymptoms of ophthalmic pathology (reduced vision, strabismus) at the age of 3.5 years. In another family, the clinical manifestations of FZD4 gene mutations were observed in two children during the first year of life (at the age of 5 and 11 months).Conclusions. The clinical picture of 3 patients with detected changes in the nucleotide sequence of the FZD4 gene is characterized by early manifestation and bilateral asymmetric ophthalmoscopic damage. The results of the study indicate the need for a timely diagnosis of FEVR in young children, recommend an interdisciplinary approach to the study of the disease, which should contribute to a better understanding of pathogenesis, and the development of an effective diagnostic, treatment and rehabilitation algorithm.

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A Case Report and Literature Review of Wilson Disease

Journal of Clinical and Nursing Research ◽

10.26689/jcnr.v4i3.1232 ◽

2020 ◽

Vol 4 (3) ◽

Author(s):

Panpan Chen ◽

Yingying Zhang ◽

Linqing Qiu ◽

Xinxin Yu

Keyword(s):

Wilson Disease ◽

Clinical Characteristics ◽

Clinical Manifestations ◽

Gene Mutations ◽

Hereditary Disease ◽

Abnormal Liver Function ◽

Atp7b Gene ◽

Literature Reference ◽

Urinary Copper

To investigate the clinical characteristics, auxiliary examination and treatment of Wilson’s disease(WD). The clinical data of a child with WD were summarized and analyzed comprehensively in conjunction with the literature reference. WD is a hereditary disease with a large age span, diverse early symptoms, high misdiagnosis rate, abnormal liver function, decreased ceruloplasmin, increased urinary copper, K-F rings, ATP7B gene mutation, ATP7B gene mutations, and abnormalities in abdominal and cranial brain imaging, which can be clearly diagnosed and require lifelong treatment. WD can be diagnosed according to the clinical manifestations and auxiliary examination to reduce misdiagnosis. The timely diagnosis and treatment will improve the prognosis the quality of life.

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Detection of EGFR Gene Mutations Using the Wash Fluid of CT-Guided Biopsy Needle in NSCLC Patients

Journal of Thoracic Oncology ◽

10.1097/jto.0b013e31816de2cd ◽

2008 ◽

Vol 3 (5) ◽

pp. 472-476 ◽

Cited By ~ 31

Author(s):

Hiroki Otani ◽

Shinichi Toyooka ◽

Junichi Soh ◽

Hiromasa Yamamoto ◽

Hiroshi Suehisa ◽

...

Keyword(s):

Gene Mutations ◽

Ct Guided ◽

Biopsy Needle ◽

Egfr Gene ◽

Guided Biopsy ◽

Ct Guided Biopsy ◽

Nsclc Patients

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Abstract 057: Cellular and Genetic Causes of Idiopathic Hyperaldosteronism

Hypertension ◽

10.1161/hyp.70.suppl_1.057 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Kei Omata ◽

Fumitoshi Satoh ◽

Ryo Morimoto ◽

Sadayoshi Ito ◽

Yuto Yamazaki ◽

...

Keyword(s):

Somatic Mutations ◽

Clinical Manifestations ◽

Gene Mutations ◽

Median Number ◽

Zona Glomerulosa ◽

Potential Contribution ◽

Unilateral Adrenalectomy ◽

Aldosterone Synthase ◽

Formalin Fixed Paraffin Embedded ◽

Idiopathic Hyperaldosteronism

Background: Primary aldosteronism (PA) affects ~10% of hypertensive patients and has unilateral and bilateral forms (30%:70%). Unilateral PA is caused by aldosterone-producing adenomas (APA), which express CYP11B2 (aldosterone synthase) and frequently harbor somatic mutations in aldosterone regulating genes ( KCNJ5>>CACNA1D ). We recently demonstrated that adrenals from normotensive patients present with pockets of cell expressing aldosterone synthase (CYP11B2). These aldosterone-producing foci (APF) have somatic gene mutations similar to those found in APA ( CACNA1D >> KCNJ5 ). Bilateral PA, which is typically treated by mineralocorticoid receptor (MR) blockade rather than surgery, is termed idiopathic hyperaldosteronism (IHA). Its pathobiology is largely unknown but has been thought to be due to zona glomerulosa (ZG) hyperplasia. Methods: We studied 11 IHA patients (7 males, 4 females) who had unilateral adrenalectomy. Immunohistochemistry for CYP11B2 and next generation sequencing (NGS) targeting genes found in APA were performed on formalin fixed paraffin embedded adrenal tissue. Results were compared to previously described cohorts of 53 age-matched normotensive patients (29 males, 24 females) which were evaluated similarly. Results: CYP11B2 expression was absent from intervening ZG cells in 8/11 (73%) IHA adrenals, but all adrenals harbored at least one APF. The median number and size of APF per case were significantly larger in IHA than normotensive controls (6.1 vs 0 APF/cm 2 of adrenal cortex and 0.25 vs. 0.16 mm 2 , respectively; p<0.0001 and p<0.006). In this IHA cohort, NGS identified CACNA1D and KCNJ5 somatic mutations in 44/71 (62%) and 1/71 (1%) of APF, respectively. Interpretations. Diffuse CYP11B2 expression in adrenal ZG cells was only observed in 3/11 IHA cases, arguing against ZG hyperplasia as the major underlying pathobiology. Rather, we demonstrated increased and enlarged APF in IHA adrenals compared to normotensive controls, supporting potential contribution to the clinical manifestations of hyperaldosteronism. The frequent occurrence of aldosterone-dysregulating CACNA1D somatic mutations in APF support CACNA1D as a potential therapeutic target in IHA to complement current MR blockade approaches.

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Mutational activation of the K-ras oncogene and the effect of chemotherapy in advanced adenocarcinoma of the lung: a prospective study.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.1.285 ◽

1997 ◽

Vol 15 (1) ◽

pp. 285-291 ◽

Cited By ~ 63

Author(s):

S Rodenhuis ◽

L Boerrigter ◽

B Top ◽

R J Slebos ◽

W J Mooi ◽

...

Keyword(s):

Lung Cancer ◽

Clinical Characteristics ◽

Gene Mutations ◽

Close Relative ◽

Ras Gene ◽

Ras Mutation ◽

Ras Mutations ◽

Adenocarcinoma Of The Lung ◽

Response To Chemotherapy ◽

Mutational Activation

PURPOSE To determine whether the clinical course and the response to chemotherapy of patients with advanced adenocarcinoma of the lung depends on the presence or absence of a ras mutation in the tumor. Mutational activation of K-ras is a strong adverse prognostic factor in stage I or II lung cancer and laboratory studies have suggested that ras mutations lead to resistance against ionizing radiation and chemotherapy. PATIENTS AND METHODS Patients with advanced adenocarcinoma of the lung with measurable or assessable disease received chemotherapy with mesna, ifosfamide, carboplatin, and etoposide (MICE). Archival biopsies, fresh biopsies, or fine-needle aspirations were tested for the presence of ras gene mutations. Associations of ras mutations with clinical characteristics, response to chemotherapy, and survival were studied. RESULTS The presence or absence of ras gene mutations could be established in 69 of 83 patients (83%). A total of 261 courses of MICE were administered to 62 informative patients, 16 of whom were shown to have a K-ras mutation-positive tumor. The frequency of mutations (26%) and the type of mutations closely matched the pattern we have previously reported in operable disease. Patients with a ras mutation in their tumor were more likely to have a close relative with lung cancer, but other clinical characteristics, such as pattern of metastases, response, and survival, were similar between the ras mutation-positive and ras mutation-negative groups. CONCLUSION Patients with advanced lung adenocarcinoma who harbor a ras mutation may have major responses to chemotherapy and have similar progression-free and overall survival as patients with ras mutation-negative tumors. K-ras mutations may represent one of several ways in which early tumors are enabled to metastasize to distant sites.

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Detected EGFR mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis

Open Medicine ◽

10.1515/med-2016-0018 ◽

2016 ◽

Vol 11 (1) ◽

pp. 93-96 ◽

Cited By ~ 2

Author(s):

Jiang Rong ◽

Ma Chunhua ◽

Lv Yuan ◽

Mu Ning ◽

Li Jinduo ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Lung Adenocarcinoma ◽

Gene Mutation ◽

Direct Sequencing ◽

Gene Mutations ◽

Egfr Mutations ◽

Egfr Gene ◽

Sequencing Method ◽

Direct Sequencing Method ◽

Egfr Gene Mutation

AbstractObjectiveTo discuss the application of ARMS method to detect EGFR gene mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis.Methods5 cases of lung adenocarcinoma were identified with meningeal metastasis that were cleared EGFR gene mutation by gene sequencing method. From each patient 5ml cerebrospinal fluid was obtained by lumbar puncture. ARMS method was used to detect EGFR mutations in cerebrospinal fluid.Results5 samples of cerebrospinal fluid were successfully detected by ARMS method, 3 samples found that EGFR gene mutations, the mutations in line with direct sequencing method.ConclusionARMS method can be used to detect EGFR gene mutations of cerebrospinal fluid samples in lung adenocarcinoma with meningeal metastasis. But cerebrospinal fluid specimens from histological specimens, blood samples need to be confirmed by further comparative study whether there is advantage.

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