scholarly journals Evaluation of FMR1 gene mutations in Turkish women newly diagnosed with primary ovarian failure

2019 ◽  
Vol 8 (2) ◽  
pp. 420
Author(s):  
Esma Sarıkaya ◽  
Aytekin Tokmak ◽  
Esra Şükran Çakar ◽  
Gürhan Güney ◽  
Neslihan Düzkale ◽  
...  
Keyword(s):  
Polymerase Chain Reaction Amplification ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Molecular Genetic Analysis ◽  
Ovarian Failure ◽  
Lymphocyte Culture ◽  
Fmr1 Gene ◽  
Newly Diagnosed ◽  
Turkish Women ◽  
Fmr1 Premutation

Background: One of the known causes of ovarian dysfunction is fragile X mental retardation gene 1 (FMR1) premutation. The prevalence of FMR1 premutation in primary ovarian failure (POF) cases may differ between the studies due to some reasons including POF definition, definition of premutation, and determination of study population, ethnicity, genetic and environmental factors. In this study authors aimed to determine the prevalence of FMR1 mutations in patients who applied to present clinic and diagnosed as POF.Methods: This retrospective cohort study was conducted on 200 women who had been newly diagnosed with POF in present clinic between 2013 and 2014. The presence of cytogenetic fragility was firstly investigated in all patients by using the lymphocyte culture method, and molecular analysis of the FMR1 gene was then performed. Genomic DNA’s of cases were isolated using standard protocols, followed by polymerase chain reaction amplification with an appropriate program. Fragment analysis of the amplification products were performed by agarose gel electrophoresis.Results: Cytogenetic analysis results in 200 cases were numerically and structurally normal in all patients, and as a result of molecular genetic analysis of FMR1 gene; 1 (0.5%) patient had complete mutation and 9 (4.5%) patients had premutation carriage.Conclusions: FMR1 gene mutations are common in women with POF. These mutations should be investigated in all patients presenting with POF, particularly in cases with early onset and family history of POF, and also genetic counseling should be given to those patients.

Characterization of plasminogen variants in healthy subjects and plasminogen mutants in patients with inherited plasminogen deficiency by isoelectric focusing gel electrophoresis

2004 ◽  
Vol 92 (08) ◽  
pp. 352-357 ◽  
Author(s):  
Katrin Tefs ◽  
Maria Georgieva ◽  
Stefan Seregard ◽  
Campbell Tait ◽  
Lori Luchtman-Jones ◽  
...  
Keyword(s):  
Isoelectric Focusing ◽  
Gel Electrophoresis ◽  
Healthy Subjects ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Molecular Genetic Analysis ◽  
Compound Heterozygous ◽  
Wild Type ◽  
Ligneous Conjunctivitis

SummaryPlasmin(ogen) plays an important role in fibrinolysis and wound healing. Severe hypoplasminogenemia has recently been linked to ligneous conjunctivitis. Plasminogen (plg) is known as a polymorphic protein and most of these variants have been identified using isoelectric focusing (IEF) gel electrophoresis. Here, we studied common plg variants from healthy subjects and plg mutants from three patients with hypoplasminogenemia and three subjects with dysplasminogenemia by molecular genetic analysis and IEF. Analysis of 24 healthy subjects showed that subjects with the most common IEF plg phenotype A (n = 12) were homozygous for aspartate at position 453 (453D), while both subjects with IEF plg phenotype B were homozygous for asparagine at this position (453N). Subjects with IEF plg phenotype AB (n = 10) were compound-heterozygous for 453D/453N. Three patients with severe hypoplasminogenemia and different plg gene mutations exhibited characteristic “abnormal” IEF band patterns when compared with IEF plg phenotypes A and B. In all heterozygous family members the observed IEF plg phenotype was derived from the wild type plg molecule only, probably due to low concentration of the mutant plg molecule in plasma. In contrast, in three unrelated subjects with heterozygous dysplasminogenemia an equal “mixture” of wild type and mutant plg was found by IEF analysis. In conclusion, plg phenotyping by IEF in combination with molecular analysis of the plg gene seems to be a useful method for characterization of plg variants and mutants.

Spectrum and frequency of GJB2 (Cx26) gene mutations in patients with hearing impairments in the Republic of Buryatia

2021 ◽  
pp. 26-36
Author(s):  
В.Г. Пшенникова ◽  
А.М. Чердонова ◽  
Ф.М. Терютин ◽  
Г.П. Романов ◽  
А.В. Соловьев ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Gene Mutations ◽  
Total Sample ◽  
Molecular Genetic Analysis ◽  
Gjb2 Gene ◽  
Hearing Impairments ◽  
C 23 ◽  
Syndromic Hearing Loss ◽  
The Republic ◽  
Biallelic Mutations

В диагностике наследственной несиндромальной потери слуха высокую информативность обеспечивают методы молекулярно-генетического анализа мутаций гена GJB2 (Cx26). Впервые в Республике Бурятия (Восточная Сибирь) путем прямого секвенирования были определены спектр и частота мутаций гена GJB2 у 165 индивидов с нарушениями слуха. В обследованной выборке было обнаружено 13 известных аллельных вариантов гена GJB2 (c.-254C>T, c.-49G>A, c.-23+1G>A, c.35delG, c.79G>A, c.101T>C, c.109G>A, c.235delC, c.299_300delАТ, c.327_328delinsA, c.341A>G, c.457G>A и c.516G>C). У пациентов бурятов мутационный спектр был представлен пятью патогенными GJB2-вариантами: c.-23+1G>A (4,1%), c.109G>A (0,6%), c.235delC (1,4%), c.327_328delGGinsA (0,6%), c.516G>C (0,6%). Среди русских пациентов было обнаружено пять мутаций: c.35delG (25,7%), c.-23+1G>A (3,3%), c.101Т>С (0,6%), c.109G>A (1,9%), c.299_300delАТ (0,6%). Вклад биаллельных мутаций гена GJB2 в этиологию потери слуха в общей выборке пациентов из Бурятии составил 15,8% (26/165). При распределении пациентов по этнической принадлежности вклад биаллельных мутаций гена GJB2 в этиологию потери слуха у русских составил 28,9% (22/76), в то время как у бурятов лишь 5,1% (4/79). Таким образом, результаты нашего исследования свидетельствуют о том, что мутации гена GJB2 не являются основной причиной потери слуха у бурятов. Вероятно, у большей части GJB2-негативных пациентов потеря слуха может быть обусловлена мутациями в других генах, ответственных за развитие наследственных нарушений слуха. In the diagnosis of hereditary non-syndromic hearing loss (HL), the methods of molecular genetic analysis of the GJB2 (Cx26) gene mutations provide high valuable information. For the first time, in the Republic of Buryatia (Eastern Siberia), the spectrum and frequency of GJB2 gene mutations were determined in a sample of 165 individuals with HL using sequencing of significant regions of the GJB2 gene. A total of 13 known allelic variants were found (c.-254C>T, c.-49G>A, c.-23+1G>A, c.35delG, c.79G>A, c.101T>C, c.109G>A, c.235delC, c.299_300delAT, c.327_328delinsA, c.341A>G, c.457G>A u c.516G>C). In the sample of Buryat patients, the mutation spectrum was represented by five GJB2 variants: c.-23+1G>A (4.1%), c.109G>A (0.6%), c.235delC (1.4%), c.327_328delGGinsA (0.6%), c.516G>C (0.6%). Five mutations were found among Russian patients: c.35delG (25.7%), c.-23+1G>A (3.3%), c.109G>A (1.9%), c.101T>C (0.6%), c.299_300delAT (0.6%). In general, the contribution of biallelic mutations of the GJB2 gene to the etiology of HL in the total sample of patients in Buryatia was 15.8% (26/165). When the total sample of patients was divided by ethnicity the contribution of biallelic mutations of the GJB2 gene to the etiology of HL in Buryat patients was 5.1% (4/79), and in Russian patients - 28.9% (22/76). Thus, the results of our study indicate that the mutations in the GJB2 gene are not the main cause of HL in Buryats. Probably, in some GJB2-negative patients (84.2% in our study), HL may be due to the mutations in other genes responsible for the development of hereditary hearing impairments.

scholarly journals Identification of missense and synonymous variants in Iranian patients suffering from autosomal dominant polycystic kidney disease

2020 ◽  
Author(s):  
Fatemeh Khadangi ◽  
Adam Torkamanzehi ◽  
Mohammad Amin Kerachian
Keyword(s):  
Kidney Disease ◽  
Genetic Analysis ◽  
Autosomal Dominant ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Molecular Genetic Analysis ◽  
Polycystic Kidney ◽  
Pkd1 Gene ◽  
Autosomal Dominant Polycystic Kidney ◽  
Iranian Patients

Abstract Background: Autosomal dominant polycystic kidney disease (ADPKD), the predominant type of inherited kidney disorder, occurs due to PKD1 and PKD2 gene mutations. ADPKD diagnosis is made primarily by kidney imaging. However, molecular genetic analysis is required to confirm the diagnosis. It is critical to perform a molecular genetic analysis when the imaging diagnosis is uncertain, particularly in simplex cases (i.e., a single occurrence in a family), in people with remarkably mild symptoms, or in individuals with atypical presentations. The main aim of this study is to determine the frequency of PKD1 gene mutations in Iranian patients with ADPKD diagnosis. Methods: Genomic DNA was extracted from blood samples from 22 ADPKD patients, who were referred to the Qaem Hospital in Mashhad, Iran. By using appropriate primers, 16 end exons of PKD1 gene that are regional hotspots, were replicated with PCR. Then, PCR products were subjected to DNA directional Sanger sequencing. Results: The DNA sequencing in the patients has shown that exons 35, 36 and 37 were non- polymorphic, and that most mutations had occurred in exons 44 and 45. In two patients, an exon-intron boundary mutation had occurred in intron 44. Most of the variants were missense and non-synonymous types. Conclusion: In the present study, we have shown the occurrence of nine novel missense or synonymous variants in PKD1 gene. These data could contribute to an improved diagnostic and genetic counseling in clinical settings.

scholarly journals Cardiac Melanoma Metastasis with ERBB2 Gene Amplification: A Potential for Future Targeted Therapy

2021 ◽  
pp. 622-627
Author(s):  
Polona Gams ◽  
Zvezdana Dolenc Stražar ◽  
Maja Šoštarič ◽  
Matic Bošnjak ◽  
Juš Kšela
Keyword(s):  
Gene Amplification ◽  
Histopathological Examination ◽  
Molecular Genetic ◽  
Gastroesophageal Junction ◽  
Gene Mutations ◽  
Molecular Genetic Analysis ◽  
Cardiac Tumors ◽  
Melanoma Metastasis ◽  
Erbb2 Gene ◽  
History Of

Cardiac tumors are rare, and their treatment differs interindividually regarding the histopathological proprieties and the stage of disease. Authors present a case of symptomatic cardiac melanoma metastasis that expressed an <i>ERBB2</i> (<i>HER2</i>) gene amplification in a course of the disease that has not yet been reported. The frail patient with a history of pulmonary and renal carcinoma, was admitted to the hospital due to a symptomatic left atrial tumor mass. The patient underwent a tumor-resecting cardiac surgery. At first mistaken for myxoma on echocardiography, the histopathological examination of the tumor revealed a melanoma of acral or mucosal origin. The melanoma metastasis was negative for common genetic mutations in <i>BRAF</i>, <i>NRAS</i> or <i>KIT</i> genes, and for the presence of <i>NTRK</i> genes fusions, but carried <i>ERBB2</i> (<i>HER2</i>) gene amplification. The absence of standard gene mutations rendered it unresponsive to treatment with BRAF and MEK inhibitors. This molecular finding is rare in melanomas and represented a therapeutic target for off-label systemic treatment with drugs, primarily aimed at ERBB2 positive breast, gastric, and gastroesophageal junction cancers. A rare finding like this justifies molecular genetic analysis of unusual tumor specimen and guarantees optimal treatment for uncommon types of cardiac metastatic tumors.

Molecular-genetic verification and treatment of neonatal diabetes mellitus related to the defects in ATP-dependent potassium channels: Results of the observation of 9 patients and the first description of ABCC8 gene mutations in Russia

2011 ◽  
Vol 57 (2) ◽  
pp. 3-8
Author(s):  
I I Dedov ◽  
Iu V Tikhonovich ◽  
Elena E Petriaikina ◽  
I G Rybkina ◽  
I É Volkov ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Pancreatic Beta Cells ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Neonatal Diabetes ◽  
Molecular Genetic Analysis ◽  
Neonatal Diabetes Mellitus ◽  
Molecular Genetic Study ◽  
Abcc8 Gene ◽  
Sound Therapy

Introduction of the methods for molecular-genetic analysis into clinical practice has opened up new prospects for both diagnosis and pathogenetically sound therapy of neonatal diabetes mellitus. It is currently known that the overwhelming majority of the cases of diabetes mellitus developing in children during the first six month of life are associated with defects of the genes controlling formation, development, and functional activity of pancreatic beta-cells whereas type 1 diabetes mellitus of autoimmune origin accounts for less than 1% of this pathology. This paper reports the results of a molecular-genetic study of 14 patients presenting with neonatal diabetes mellitus. Nine cases are shown to have developed as a result of mutations in KCNJ11 and ABCC8 genes. ABCC8 mutations are described for the first time in Russia. Analysis of clinical forms of neonatal diabetes mellitus revealed correlation between the type of mutations, clinical features of the disease, and susceptibility of the patients to sulfonylurea drugs.

scholarly journals Monogenic diabetes associated with PAX4 gene mutations (MODY9): first description in Russia

2017 ◽  
Vol 20 (5) ◽  
pp. 384-387
Author(s):  
Natalya A. Zubkova ◽  
Olesya A. Gioeva ◽  
Vasiliy M. Petrov ◽  
Evgeny V. Vasiliev ◽  
Alexei V. Timofeev ◽  
...  
Keyword(s):  
Pancreatic Beta Cells ◽  
Novel Mutation ◽  
Pancreatic Beta Cell ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Russian Literature ◽  
Molecular Genetic Analysis ◽  
Dominant Type ◽  
Genetic Characteristics ◽  
Monogenic Diseases

Maturity-onset diabetes of the young (MODY) is a heterogeneous group of disorders characterised by autosomal dominant type of inheritance and caused by genetic defects leading to dysfunction of pancreatic beta-cells. To date, at least 13 subtypes of MODY have been described in the literature, the most frequent of which are MODY types 13. MODY2 and MODY3 are the most prevalent subtypes, and were previously described in our country, Russia. Several cases of rare MODY subtypes were subsequently described in the Russian literature. The current report is the first in the Russian literature to present clinical and molecular genetic characteristics of two cases of another rare MODY subtypeMODY9. This type of MODY is associated with mutations in the PAX4 gene, which encodes transcription factor PAX4, one of the factors essential for pancreatic beta-cell differentiation. Molecular genetic analysis was performed using next-generation sequencing, a new method recently applied to verify monogenic diseases and, in particular, MODY. This study reports a novel mutation in the PAX4 gene in MODY patients.

scholarly journals Identification of Novel Nonsense Mutations in Iranian patients suffering from autosomal dominant polycystic kidney disease

2019 ◽  
Author(s):  
Fatemeh Khadangi ◽  
Adam Torkamanzehi ◽  
Mohammad Amin Kerachian
Keyword(s):  
Kidney Disease ◽  
Genetic Analysis ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Molecular Genetic Analysis ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Iranian Patients

Abstract Background: Autosomal dominant polycystic kidney disease (ADPKD) is the predominant type of inherited kidney disorder, which occurs due to PKD1 and PKD2 gene mutations. ADPKD diagnosis is made primarily by kidney imaging; however, molecular genetic analysis needs to be implicated to confirm the diagnosis. It is critical to perform a molecular genetic analysis when the diagnosis is uncertain, particularly in simplex cases (i.e., a single occurrence in a family), in people with remarkably mild symptoms, or in individuals with atypical presentations. The main aim of this study is to determine the likelihood of PKD1 gene mutations in Iranian patients with ADPKD diagnosis. Methods: Genomic DNA was isolated from blood samples from 26 ADPKD patients, who were referred to the Qaem Hospital in Mashhad, Iran. By using suitable primers, 16 end exons of PKD1 gene that are regional hotspots, were replicated with PCR. Then, PCR products were subjected to DNA directional Sanger sequencing.Results: The results of DNA sequencing in the patients showed that exons 35, 36 and 37 were non- polymorphic, while most mutations had occurred in exons 44 and 45. Only in two patients, exon-intron boundary mutation had occurred in intron 44. Most of the variants were missense and non-synonymous types. Conclusion: In this study, we present nine novel mutations/polymorphisms in PKD1. These data will contribute to an improved diagnostic and genetic counseling in clinical settings. Keywords: Autosomal dominant polycystic kidney disease; PKD1; mutational analysis; Iranian

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