scholarly journals Joubert's syndrome as a cause of cholestasis in children

2020 ◽  
pp. 64-71
Author(s):  
V.S. Berezenko ◽  
◽  
H.Z. Mikhailyuk ◽  
Keyword(s):  
Molecular Genetic ◽  
Gene Mutations ◽  
Joubert Syndrome ◽  
Watch Glass ◽  
Cholestatic Liver Disease ◽  
Large Head ◽  
Palmar Erythema ◽  
Genetic Examination ◽  
Molecular Genetic Test ◽  
Chronic Intrahepatic Cholestasis

Literature review and a case report of Joubert syndrome in a preschool child are presented. This syndrome is accompanied by chronic intrahepatic cholestasis, characteristic facial dysmorphia, congenital malformations of the urinary system, eyes pathology, confirmed by a molecular genetic test of TMEM67 gene mutations. Diagnostic aspects of this pathology have been reviewed. The clinical case description. Boy K was admitted to the pediatric hepatology department with respiratory and renal failure, decompensated acidosis. On admission, complaints included shortness of breath, severe itching, pale and dry skin, poor appetite and delayed physical development. On examination, dysembryogenic stigmas: large head circumference, elongated face, protruding forehead, high rounded eyebrows, deeply set eyes, hypertelorism, antimongoloid incision of the eyes, low auricles. The skin was pale, dry with the scratch marks on the arms and legs flexor surfaces. Ankles, wrists skin lichenification, bruising and hyperpigmentation was observed. Moderate palmar erythema, spider veins on the abdomen, watch-glass nails were present. The abdomen was enlarged due to hepatosplenomegaly. A clinical and paraclinical examination was conducted, the patient was consulted by related specialists. Based on the obtained data and molecular genetic examination, the diagnosis was made. Conclusion. Joubert's syndrome may have a clinical presentation similar to that in cholestatic liver disease with typical clinical and laboratory symptoms. The molecular genetic testing is an important workup component in children with liver pathology combined with damage to other organs and systems. Successful treatment is possible providing a multidisciplinary approach used. The study was conducted by the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the abovementioned institution. Informed consent of the child's parents was obtained for the research. The authors declare no conflict of interest. Keywords: Joubert syndrome, cholestasis, children.

scholarly journals A clinical case of neonatal diabetes caused by INS gene mutation

2019 ◽  
Vol 22 (2) ◽  
pp. 170-176
Author(s):  
Rosa A. Atanesyan ◽  
Tatyana A. Uglova ◽  
Tatyana M. Vdovina ◽  
Leonid Ya. Klimov ◽  
Marina U. Kostanova ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Clinical Case ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Gene Mutations ◽  
Neonatal Diabetes ◽  
Compound Heterozygous ◽  
Pancreatic Cell ◽  
Cell Dysfunction ◽  
Genetic Examination

Neonatal diabetes mellitus (NDM) is a severe endocrine pathology diagnosed in children during the first months of life. It comprises rare (1:300 0001:400 000 newborns) metabolic disorders with postnatal pancreatic -cell dysfunction, manifested by hyperglycaemia and hypoinsulinaemia. It is currently established that molecular genetic diagnosis of neonatal diabetes forms can influence treatment and prognosis. Interestingly, most identified mutations in the insulin gene are not inherited, but are sporadic. There is evidence that, in addition to heterozygous INS mutations, NDM can be caused by homozygous or compound-heterozygous mutations. The present article presents the clinical case of a girl with NDM associated with an INS gene mutation. INS gene mutations cause permanent diabetes and require children to undergo genetic examination, especially patients with type 1 diabetes in the absence of antibodies. Currently, there are no data that allow to determine a phenotypic and genotypic portrait of NDM forms or to explain the factors determining their occurrence. Further studies of clinical cases of neonatal diabetes are therefore required to determine the characteristics of NDM subtypes with subsequent disease prognosis.

Clinical application of polymorphic variants of the genes ESR1 and CYP2D6*4 in patients with breast and endometrial cancer

2017 ◽  
pp. 132-138
Author(s):  
O.V. Paliychuk ◽  
◽  
L.Z. Polishchuk ◽  
Z.I. Rossokha ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endometrial Cancer ◽  
Hormone Therapy ◽  
Molecular Genetic ◽  
Cancer Syndrome ◽  
Genetic Characteristics ◽  
Multiple Tumors ◽  
Receptor Status ◽  
Genetic Examination ◽  
The Impact

The objective: determining gene polymorphism features ERS1, CYP2D6 in patients with breast cancer (RHZ) and endometrial cancer (EC) and the impact assessment studied genetic characteristics compared to receptor status (immunohistochemical determination of expression levels of ER, PR) tumors and the results of the treatment. Patients and methods. article presents the results of complex clinical, morphological, clinical-genealogical, and molecular-genetic examination of 28 females: 19 patients with breast cancer (BC), 9 patients with endometrial cancer (EC), including 5 patients with primary-multiple tumors (PMT) with and without tumor pathology aggregation in families. Results. The It was determined that in patients’ families malignant tumors of breast, uterine body and/or ovaries prevail that corresponds to Lynch type II syndrome (family cancer syndrome). Molecular-genetic examination of genomic DNA of peripheral blood and histological sections for the presence of SNPs of ESR and CYP2D6*4 genes comparing with the results of immunohistochemical study of tumors for receptors ER and PR status have not found associations between these characteristics; although among EC patients the occurrence of genotypes 397ТТ and 351АА was significantly higher comparing with BC patients (55.55% and 10.5% for genotype 397ТТ,and 15.8% for genotype 351АА, respectively). At the same time the patients with BC and primary-multiple tumors (PMT) of female reproductive system organs (FRSO) that carried mutations in BRCA1 in all the cases demonstrated positive ER and PR receptor status and adverse combinations of polymorphous variants of the genes ESR1 (397СС, 397ТС) and CYP2D6*4 (1846G, 1846GA), suggesting combined effect of these factors on the development of malignant neoplasias of FRSO in families with positive family cancer history. In BC patients, receiving standard hormone therapy with tamoxifen, those, who had genotype 1846GG of the gene CYP2D6*4, in 3 patients (15.8%) of 19 (100%) patients disease recurrence was diagnosed. Conclusion. The obtained results allow clinical use of the assessment of polymorphism frequency of the genes ESR1 and CYP2D6*4 for selection of individual hormone therapy regimens schemes for BC patients, to increase efficacy of dispensary observation after finishing of special therapy for such patients, and also personalization of complex and combined treatment regimens. Key words: breast cancer, endometrial cancer, family cancer syndrome, single nucleotide polymorphisms (SNPs) of the genes ESR1, CYP2D6*4.

scholarly journals Novel missense mutation of SASH1 in a Chinese family with dyschromatosis universalis hereditaria

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lu Cao ◽  
Ruixue Zhang ◽  
Liang Yong ◽  
Shirui Chen ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Sequence Alignment ◽  
Multiple Sequence Alignment ◽  
Molecular Genetic ◽  
Family Members ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Mendelian Inheritance ◽  
Chinese Family ◽  
Multiple Sequence

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.

scholarly journals Development of a Web-Based Query Tool for Quality Assurance of Clinical Molecular Genetic Test Results

2007 ◽  
Vol 9 (1) ◽  
pp. 95-98 ◽  
Author(s):  
Matthew J. McGinniss ◽  
Rebecca Chen ◽  
Victoria M. Pratt ◽  
Arlene Buller ◽  
Franklin Quan ◽  
...  
Keyword(s):  
Quality Assurance ◽  
Genetic Test ◽  
Molecular Genetic ◽  
Test Results ◽  
Web Based ◽  
Genetic Test Results ◽  
Query Tool ◽  
Molecular Genetic Test

Phenotypes of professional bronchial asthma from the standpoint of spirometry

2021 ◽  
pp. 43-54
Author(s):  
Antonina G. Baykova ◽  
Marina Yuryevna Vostroknutova ◽  
Natalia A. Ostryakova ◽  
Tatyana Mikhailovna Kiryushina
Keyword(s):  
Comparative Analysis ◽  
Bronchial Asthma ◽  
Clinical Stage ◽  
Molecular Genetic ◽  
Control Group ◽  
Forced Exhalation ◽  
Choice Of Treatment ◽  
Genetic Examination

The aim of the study was to conduct a comparative analysis of spirometric indicators of respiration in various phenotypes of occupational bronchial asthma. Materials and methods. At the clinical stage of the work, a comprehensive clinical, radiological, spirographic, echocardiographic, immunological and molecular genetic examination of 170 patients of the main groups and 50 individuals of the control group was carried out. The results of the study. Dynamic determination of the speed indicators of forced exhalation in various phenotypes of occupational bronchial asthma can improve the diagnosis of obstructive disorders in this pathology, optimize the choice of treatment tactics, and predict the course of this pathology.

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

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.

scholarly journals Mutations in the genes of glutathione-S-transferase in patients with breast cancer and their close relatives living in chernivtsi region

2014 ◽  
Vol 18 (4 (72)) ◽  
Author(s):  
T. V. Kruk ◽  
O. P. Peresunko ◽  
R. A. Volkov
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Prognostic Factor ◽  
Blood Plasma ◽  
Genetic Marker ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Glutathione S Transferase ◽  
High Risk Disease ◽  
Close Relatives

Based on genotyping study of two variants (GSTP1 and GSTT1) of gene mutations glutathione-Stransferase (GST) in the blood plasma of patients with breast cancer, relatives of I degree of kinship and healthy women of Chernivtsi region, we made a conclusion as to the usefulness of this study as additional molecular genetic marker, determining high-risk disease as a prognostic factor for further observation and specifying diagnostics.

scholarly journals Werner mesomelic dysplasia

2018 ◽  
Vol 6 (4) ◽  
pp. 92-97
Author(s):  
Evgeniia A. Kochenova ◽  
Olga E. Agranovich ◽  
Svetlana I. Trofimova ◽  
Anna P. Nikitina
Keyword(s):  
Clinical Case ◽  
Regulatory Element ◽  
Molecular Genetic ◽  
Hip Dislocation ◽  
Preaxial Polydactyly ◽  
Mesomelic Dysplasia ◽  
Dominant Disease ◽  
Genetic Examination ◽  
Hands And Feet ◽  
Nasal Defects

Introduction. The term “mesomelic dysplasia” refers to a group of disorders wherein limb shortening is most pronounced in the middle segment (forearm and leg) of the extremities. Werner mesomelic dysplasia is characterized by absence or hypoplasia of the tibia, preaxial polysyndactyly on the hands and feet, as well as by triphalangeal thumbs, absence of a patella, and fibular bone dislocation. Molecular genetic causes of the disease are mutations at position 404 of the regulatory element (ZRS) of the SHH gene in the LMBR1 gene (OMIM 188740). Clinical case. A girl with triphalangeal thumbs and polydactyly of the hands, right hip dislocation, tibia hypoplasia, fibular dislocation on both sides, and preaxial polydactyly of the feet was examined and treated at the age of 1 year. Considering the clinical and radiological picture, the girl was diagnosed with Werner mesomelic dysplasia. To verify the disease, a molecular genetic examination of the child was performed. A variant of replacement of 230 T > C in the regulatory element of the ZRS of the SHH gene was discovered in the literature. Discussion. Differential diagnosis can be made with Laurin-Sandrow syndrome, which is characterized by doubling of the ulna and fibula with the absence of the radius and tibia and preaxial polydactyly/syndactyly of the hands and feet. The presence of nasal defects (particularly involving the columella) distinguishes this condition from other syndromes, which was not shown in this clinical observation. Conclusion. We report the clinical case of an autosomal-dominant disease, Werner mesomelic dysplasia, which is a rare pathology with a typical clinical picture combined with congenital hip dislocation, which was not previously described. The molecular genetic examination confirms the presence of a pathogenic variant of the ZRS element of the SHH gene, which causes the development of Werner’s mesomelic dysplasia, but the mutation variant was not registered before, which requires an additional examination of the child’s relatives.

Molecular genetic investigation of the neurofibromatosis type 2 tumor suppressor gene in sporadic meningioma

1996 ◽  
Vol 84 (5) ◽  
pp. 847-851 ◽  
Author(s):  
Takehiko Harada ◽  
Richard M. Irving ◽  
John H. Xuereb ◽  
David E. Barton ◽  
David G. Hardy ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Neurofibromatosis Type ◽  
Suppressor Gene ◽  
Neurofibromatosis Type 2 ◽  
Chromosome 22 ◽  
Sporadic Meningioma

✓ The authors investigated the role of somatic mutations of the neurofibromatosis type 2 (NF2) gene in sporadic meningioma. Neurofibromatosis 2 is a dominantly inherited familial tumor syndrome predisposing affected patients to a variety of central nervous system tumors including vestibular schwannoma and meningioma. Neurofibromatosis type 2 is caused by germline mutations in the NF2 tumor suppressor gene. In addition, the authors and others have reported that somatic NF2 gene mutations occur frequently in nonfamilial vestibular schwannoma. In this study, molecular genetic analysis was performed on 23 nonfamilial meningiomas. Paired DNA samples extracted from the blood and tumors of the patients were analyzed for loss of heterozygosity (LOH) in the region of the NF2 gene on chromosome 22 using closely linked DNA markers. The NF2 gene mutations were sought by single-stranded conformation polymorphism analysis and DNA sequencing. Fourteen (61%) of 23 meningiomas showed LOH in the region of the NF2 gene on chromosome 22. Somatic NF2 gene mutations were detected in eight meningiomas (35%) after screening all 17 exons. All tumors with NF2 gene mutations showed simultaneous chromosome 22 LOH. Review of the histopathological findings of the cases studied did not demonstrate any predominance of genetic abnormalities in a particular histological type of meningioma. These results are compatible with the hypothesis that the NF2 gene acts as a tumor suppressor and that its inactivation is important in the pathogenesis of sporadic meningioma.

scholarly journals Effective communication of molecular genetic test results to primary care providers

2012 ◽  
Vol 15 (6) ◽  
pp. 444-449 ◽  
Author(s):  
Maren T. Scheuner ◽  
◽  
Maria Orlando Edelen ◽  
Lee H. Hilborne ◽  
Ira M. Lubin
Keyword(s):  
Primary Care ◽  
Genetic Test ◽  
Molecular Genetic ◽  
Effective Communication ◽  
Primary Care Providers ◽  
Test Results ◽  
Care Providers ◽  
Genetic Test Results ◽  
Molecular Genetic Test
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