scholarly journals First Results from the Prospective German Registry for Childhood Glaucoma: Phenotype–Genotype Association

2021 ◽  
Vol 11 (1) ◽  
pp. 16
Author(s):  
Julia V. Stingl ◽  
Stefan Diederich ◽  
Heidi Diel ◽  
Alexander K. Schuster ◽  
Felix M. Wagner ◽  
...  
Keyword(s):  
Risk Factor ◽  
Molecular Genetic ◽  
Genetic Alterations ◽  
Molecular Genetic Analysis ◽  
Genetic Mutations ◽  
Buccal Swab ◽  
Novel Variants ◽  
First Results ◽  
Genetic Examination ◽  
German Registry

Childhood glaucoma is a heterogeneous disease and can be associated with various genetic alterations. The aim of this study was to report first results of the phenotype–genotype relationship in a German childhood glaucoma cohort. Forty-nine eyes of 29 children diagnosed with childhood glaucoma were prospectively included in the registry. Besides medical history, non-genetic risk factor anamnesis and examination results, genetic examination report was obtained (23 cases). DNA from peripheral blood or buccal swab was used for molecular genetic analysis using a specific glaucoma gene panel. Primary endpoint was the distribution of causative genetic mutations and associated disorders. Median age was 1.8 (IQR 0.6; 3.8) years, 64% participants were female. Secondary childhood glaucoma (55%) was more common than primary childhood glaucoma (41%). In 14%, parental consanguinity was indicated. A mutation was found in all these cases, which makes consanguinity an important risk factor for genetic causes in childhood glaucoma. CYP1B1 (30%) and TEK (10%) mutations were found in primary childhood glaucoma patients. In secondary childhood glaucoma cases, alterations in CYP1B1 (25%), SOX11 (13%), FOXC1 (13%), GJA8 (13%) and LTBP2 (13%) were detected. Congenital cataract was associated with variants in FYCO1 and CRYBB3 (25% each), and one case of primary megalocornea with a CHRDL1 aberration. Novel variants of causative genetic mutations were found. Distribution of childhood glaucoma types and causative genes was comparable to previous investigated cohorts. This is the first prospective study using standardized forms to determine phenotypes and non-genetic factors in childhood glaucoma with the aim to evaluate their association with genotypes in childhood glaucoma.

scholarly journals TOPICALITY OF FORENSIC MOLECULAR GENETIC EXAMINATION AND ISSUES REGARDING ITS PERFORMING

2018 ◽  
Vol 18 ◽  
pp. 256-263
Author(s):  
V. V. Topchiy
Keyword(s):  
Dna Analysis ◽  
Human Life ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Molecular Genetic Analysis ◽  
Present Stage ◽  
Law Enforcement Agencies ◽  
Biological Origin ◽  
Genetic Features ◽  
Genetic Examination

Modern progress in forensic molecular genetic examination allow to obtain information about a particular person using traces variety of biological origin especially while committing grave crimes against human life and health, that are usually found at the scene and belong to a human body. A significant advantage of this method under crime investigation is precisely the safe exclusion of suspected persons not involved in the commission of a crime, in identifying those who committed a crime with a high probability level. At the present stage of forensic molecular genetic examination development there are significant gaps in legislation that are solved by adopting relevant normative and legal acts and improving existing ones. Effective method for of DNA analysis development is the creation of appropriate bases of genetic features of a person. However, the legislative consolidation of this process should take place in the context of respecting and protecting personal rights. However, terms of performing molecular genetic examination significantly exceed the terms of pre-trial investigation. This problem can be solved by expanding network of laboratories that perform such examination. Despite presence of a small number of problems, it is possible to affirm that DNA analysis is the most effective and reliable of all known methods of person identification at the present stage. At present, expert molecular genetic analysis develops not only as a section of molecular genetic research but also as a complete element of criminalistic knowledge that is aimed at investigating and disclosing crimes. Therefore, implementation of molecular genetic research methods into the practice of law enforcement agencies in Ukraine will significantly increase investigation effectiveness of many serious crimes against person.

Molecular Genetic Analysis Excludes Implantation Metastasis of Basal Cell Carcinomas

2003 ◽  
Vol 127 (9) ◽  
pp. 1221-1224
Author(s):  
Christian Hafner ◽  
Arndt Hartmann ◽  
Ruth Knuechel ◽  
Wolfgang Dietmaier ◽  
Michael Landthaler ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Loss Of Heterozygosity ◽  
Basal Cell ◽  
Normal Skin ◽  
Molecular Genetic ◽  
Suppressor Gene ◽  
Genetic Alterations ◽  
Molecular Genetic Analysis ◽  
P53 Mutation ◽  
Implantation Metastasis

Abstract Basal cell carcinoma (BCC) of the skin is the most common tumor in the white population. A 66-year-old man developed 2 BCCs at the left parietal region of the head and at the helix of the left ear. The 2 lesions matched exactly when pressing the ear against the head, suggesting an implantation metastasis mechanism. Molecular genetic techniques were used to confirm or exclude such a mechanism in this rare clinical constellation. Tumor tissues were precisely microdissected for DNA isolation. Exons 5–9 of the p53 tumor suppressor gene were directly sequenced. In addition, loss of heterozygosity analysis of chromosome 9q was performed using 5 polymorphic microsatellite markers. The BCC of the ear revealed a p53 mutation at codon 273, whereas the other one lacked this mutation. In addition, the smaller BCC of the ear showed loss of heterozygosity at 9q33.3, in contrast with the larger BCC. Interestingly, histologically normal skin of the ear distant from the small BCC had the same deletion, indicating a field defect of this skin patch at 9q33.3. Molecular genetic analysis clearly demonstrated different genetic alterations of the two BCCs and therefore most likely excludes a mechanism of implantation metastasis.

Molecular genetic analysis of Turkish Gaucher's disease patients reveals three novel variants in Glucocerebrosidase (GBA) gene

Meta Gene ◽  
2020 ◽  
Vol 25 ◽  
pp. 100725
Author(s):  
Gizem Önal ◽  
Ersin Gümüş ◽  
Hülya Demir ◽  
Aysel Yüce ◽  
Serap Dökmeci (Emre)
Keyword(s):  
Genetic Analysis ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Gaucher's Disease ◽  
Gaucher’S Disease ◽  
Novel Variants ◽  
Gba Gene

scholarly journals HUMAN BEING AS THE BEARER OF IDENTIFYING BIOLOGICAL INFORMATION

2021 ◽  
Author(s):  
L. Кotliarenko ◽  
А. Коfanov ◽  
O. Коfаnоvа ◽  
V. Zherebak
Keyword(s):  
Genetic Analysis ◽  
Dna Analysis ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Molecular Genetic Analysis ◽  
Genetic Identification ◽  
Criminal Proceedings ◽  
Genetic Traits ◽  
Criminal Offenses ◽  
Genetic Examination

In forensic practice, biological traces of a person are very often used as material evidence - blood, hair, saliva, semen, urine, sweat, as well as parts of organs and tissues. Establishing the origin of these traces from a specific person is very important for the investigation of criminal offenses. The current level of development of molecular genetic research indicates the need to use DNA analysis in the detection and investigation of criminal offenses against a person. Today, molecular genetic identification reveal reliable prospects for solving identification problems in the criminal proceedings and developing the evidence base, and also has a number of advantages over traditional serological methods for studying human biological traces. It should be noted that along with the traditional method of nuclear DNA research, mitochondrial DNA research is also being carried out, which allows solving the problem of molecular genetic examination to establish biological affinity. The value of this method lies in its effectiveness in the study of a small amount of degraded DNA, secretions and heavily damaged objects, the study of which is impossible by traditional methods. When performing a forensic molecular genetic examination for the full identification of the detected traces when examining the places of committed criminal offenses, comparative samples are important, as well as the selection of appropriate biological samples to establish paternity and family ties. Molecular genetic analysis of DNA is only one of the stages of identification, and in order to arrive at the final result, a statistical analysis of the data obtained is necessary, which is especially important when the genotypes of the criminal and the suspect in mixed tracks coincide. For a probable-statistical assessment of the results of the identification significance of the set of established genetic traits, the frequencies of the distribution of the studied alleles in the population are required. Today, the DNA analysis method has become one of the most demanded directions in the development of forensic examinations, and its results are quite reliable evidence of the involvement of a specific person in a crime. Due to its unique capabilities, molecular genetic analysis of DNA is a powerful tool in the investigation of criminal proceedings.

Systemic Pseudohypoaldosteronism Type 1 due to 3 Novel Mutations in SCNN1Aand SCNN1BGenes

2019 ◽  
Vol 91 (3) ◽  
pp. 175-185
Author(s):  
Atilla Cayir ◽  
Yasar Demirelli ◽  
Duran Yildiz ◽  
Hasan Kahveci ◽  
Oguzhan  Yarali ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Genetic Analysis ◽  
Molecular Genetic ◽  
Autosomal Recessive Disorder ◽  
Plasma Renin ◽  
Molecular Genetic Analysis ◽  
Organ Systems ◽  
Novel Variants ◽  
Pseudohypoaldosteronism Type

Objective: The systemic form of pseudohypoaldosteronism type 1 (PHA1) is an autosomal recessive disorder characterized by defective sodium transport in multi-organ systems. Mutations in the genes encoding the amiloride-sensitive epithelial sodium channel, ENaC, account for genetic causes of systemic PHA1. We describe systemic PHA1 due to 4 novel variants detected in SCNN1A and SCNN1B in 3 cases from 3 unrelated consanguineous families. Patients and Methods: We evaluated the clinical presentations, biochemical and hormonal characteristics, and molecular genetic analysis results of 3 patients from 3 unrelated consanguineous families and parents from whom samples were available. Results: The ages at presentation were postnatal days 9, 10, and 5. The main presentation symptoms were vomiting, poor feeding, weakness, weight loss, and skin rash. All patients exhibited laboratory characteristics including severe hyponatremia, hyperkalemia, metabolic acidosis, elevated plasma renin, elevated aldosterone, and positive sweat tests, suggesting a diagnosis of systemic PHA1. Molecular genetic analysis revealed 2 novel pathogenic variants [c.87C>A(p.Tyr29*)/IVS9 + 1G>A (c.1346 + 1G>A)] in SCNN1Bin case 1, a novel homozygous pathogenic variant [p.His69Arg(c.206A>G] in SCNN1Ain case 2, and a homozygous one-base duplication, p.A200Gfs*6 (c.598dupG), in SCNN1A in case 3. Conclusion: PHA1 should be considered at differential diagnosis in patients presenting with hyponatremia, hyperkalemia, and metabolic acidosis. The cases in this report involving 4 novel variants will add valuable insights into the phenotype-genotype relationship and will expand the mutation database.

scholarly journals IDENTIFICATION OF A PERSON BY THE DNA OF THE PULP OF THE TOOTH

2018 ◽  
Vol 25 (6) ◽  
pp. 154-159
Author(s):  
S. V. Syrak ◽  
I. A. Gatilo ◽  
Yu. S. Mazevskaya
Keyword(s):  
Genetic Analysis ◽  
Genetic Information ◽  
High Probability ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Tooth Pulp ◽  
Bone Powder ◽  
Tooth Number ◽  
Genetic Examination ◽  
Relationship Of

Aim. The study was designed for conducting a molecular genetic analysis of DNA of the tooth pulp and establishing the genetic relationship of the child and the parent.Materials and methods. The tooth number 16 of the claimed father was provided for the DNA extraction. Saliva samples and DNA preparations of the prospective daughter were obtained for the study. In the course of the research, the M-sorbbone reagent kit was used to isolate DNA from the bone powder.Results. The conducted studies have shown that the DNA preparations isolated from a tooth and the N sample of saliva have the following genotypic allelic combinations. It was established that for each of the studied STP systems in the genome of the claimed father an allele is found, which formally coincides with the allele of conditionally paternal (nonmaternal) origin in the child’s genome.Conclusion. As shown by the results of the study, the only carrier of DNA in a forensic medical molecular genetic examination, in this case, was a tooth, namely, pulp, which was protected by the durable tissues – dentin and enamel. The uniqueness of this case lies in the fact that it is the pulp that is the only tissue that retains the genetic information making it possible to state the high probability of the claimed relationship of the father and the child.

scholarly journals Generalizált epilepszia hátterében azonosított ioncsatorna-génmutáció ritka formája

2019 ◽  
Vol 160 (21) ◽  
pp. 835-838 ◽  
Author(s):  
Ágnes Till ◽  
Renáta Szalai ◽  
Márta Hegyi ◽  
Erzsébet Kövesdi ◽  
Gergely Büki ◽  
...  
Keyword(s):  
Potassium Chloride ◽  
Molecular Genetic ◽  
Genetic Alterations ◽  
Epilepsy Syndrome ◽  
Idiopathic Generalized Epilepsy ◽  
Whole Exome ◽  
Genetic Examination ◽  
Neurocutaneous Syndrome ◽  
Extended Area ◽  
Generalized Epilepsy

Abstract: The advances in molecular genetic methods has lead to the discovery of the genetic alterations that underlie the etiology of most diseases previously held to be idiopathic. Targeted genetic examination of a pediatric male patient showing a normal intellect, an extended area of skin hypopigmentation, and suffering from generalized epilepsy displaying a switch in epilepsy syndrome during the course of the disease towards a neurocutaneous syndrome was unsuccessful. Whole-exome sequencing identified a heterozygous missense mutation in a potassium chloride cotransporter gene, which together with the phenotype underscores the diagnosis of an epilepsy syndrome known in the literature as idiopathic generalized epilepsy type 14. Orv Hetil. 2019; 160(21): 835–838.

scholarly journals Two Novel Compound Heterozygous Pathogenic Variants in P2YR12 gene

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1154-1154
Author(s):  
Arnaud Dupuis ◽  
Doris Böckelmann ◽  
Patricia Laeuffer ◽  
Katharina Neubauer ◽  
Christian Gachet ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Platelet Aggregation ◽  
Molecular Genetic ◽  
Index Patient ◽  
Molecular Genetic Analysis ◽  
Compound Heterozygous ◽  
Twin Brother ◽  
Pathogenic Variants ◽  
Fibrinogen Binding ◽  
Novel Variants

Abstract Introduction: P2Y12 receptor (P2Y12R) defect is a rare hemorrhagic disorder characterized by mild to moderate bleeding diathesis with easy bruising, mucosal bleedings, and excessive post-operative hemorrhage. It is due to mutations of the P2YR12 gene resulting in impairment of platelet responses to adenosine 5'-diphosphate (ADP) and subsequently to any other agonist as ADP is secreted from the dense granules during platelet activation. The P2Y12R plays a key role in platelet aggregation by amplifying the platelet activation process which is necessary to ensure appropriate primary hemostasis. The activation of the P2Y12R by ADP results in inhibition of adenylyl cyclase (AC) and in activation of phosphoinositide 3-kinase (PIK3), which amplifies and sustains the platelet aggregation response. To date only 12 pathogenic variants in the P2YR12 gene are listed in the Human Gene Mutation Database (HGMD®) (10 missense/nonsense mutations and 2 small deletions). Seven missense mutations are described in the literature in patients suffering from bleeding disorders of various severity. Autosomal recessive (homozygous and compound heterozygous pathogenic variants) as well as autosomal dominant (only one heterozygous pathogenic variant) inheritance has been reported. Patients and Methods: We investigated an 8 year old index patient who came to our outpatient clinic to investigate an increased bleeding tendency. He suffered from easy bruising and reported increased bleeding after tonsillectomy. His twin brother was also affected regarding bleeding disorder. Their father suffered sometimes from epistaxis, their mother and three older siblings were clinically unaffected. Platelet functions were assessed by light transmission aggregometry using citrated PRP. Membrane glycoprotein quantification, fibrinogen binding, von Willebrand factor (VWF) binding and the VASP assay were performed by flow cytometry. Molecular genetic analysis (Sanger sequencing) was performed for all exons including UTR regions and splice sites of the P2RY12-gene (NM_002788.4) for the twins and their parents. Results: The index patient and his brother showed normal values for platelet count, aPTT, INR, FXIII and VWF parameters. Both twins showed impaired platelet aggregation after stimulation with collagen, ADP and epinephrine. For both the index patient and his twin brother ADP (4-20 µM and 4-10 µM respectively) induced aggregation was markedly reduced and rapidly reversible. Flow cytometry revealed severely decreased fibrinogen binding for the index patient and his twin brother after stimulation with ADP (0.25-5.0 μmol/l) compared to control platelets. For CD42a/b (GP Ib/IX-complex), CD41 (GP IIb/IIIa-complex), ristocetin-induced VWF-binding, CD62- and CD63-expression, normal values were measured. The VASP assay revealed a strong defect with a PRI value of patient's platelets as low as 1.2% and 1% respectively (normal range > 69%). Molecular genetic analysis revealed two novel variants in the P2YR12 coding sequence (Tab.1). Conclusion: We have identified two novel variants in the P2YR12 gene with pathogenic predictions in a compound heterozygous state in twin brothers suffering from a chronic bleeding disorder. Flow cytometry analyses (fibrinogen binding) and VASP analyses are valuable tools to diagnose a platelet ADP-receptor defect. Table Table. Disclosures No relevant conflicts of interest to declare.

Molecular genetic markers for thyroid FNAB

2015 ◽  
Vol 54 (03) ◽  
pp. 94-100 ◽  
Author(s):  
P. B. Musholt ◽  
T. J. Musholt
Keyword(s):  
Genetic Markers ◽  
Thyroid Nodules ◽  
Molecular Genetic ◽  
Genetic Alterations ◽  
Diagnostic Tools ◽  
Ultrasound Screening ◽  
Thyroid Malignancy ◽  
Thyroid Carcinomas ◽  
Molecular Genetic Markers ◽  
The Impact

SummaryAim: Thyroid nodules > 1 cm are observed in about 12% of unselected adult employees aged 18–65 years screened by ultrasound scan (40). While intensive ultrasound screening leads to early detection of thyroid diseases, the determination of benign or malignant behaviour remains uncertain and may trigger anxieties in many patients and their physicians. A considerable number of thyroid resections are consecutively performed due to suspicion of malignancy in the detected nodes. Fine needle aspiration biopsy (FNAB) has been recommended for the assessment of thyroid nodules to facilitate detection of thyroid carcinomas but also to rule out malignancy and thereby avoid unnecessary thyroid resections. However, cytology results are dependent on experience of the respective cytologist and unfortunately inconclusive in many cases. Methods: Molecular genetic markers are already used nowadays to enhance sensitivity and specificity of FNAB cytology in some centers in Germany. The most clinically relevant molecular genetic markers as pre-operative diagnostic tools and the clinical implications for the intraoperative and postoperative management were reviewed. Results: Molecular genetic markers predominantly focus on the preoperative detection of thyroid malignancies rather than the exclusion of thyroid carcinomas. While some centers routinely assess FNABs, other centers concentrate on FNABs with cytology results of follicular neoplasia or suspicion of thyroid carcinoma. Predominantly mutations of BRAF, RET/PTC, RAS, and PAX8/PPARγ or expression of miRNAs are analyzed. However, only the detection of BRAF mutations predicts the presence of (papillary) thyroid malignancy with almost 98% probability, indicating necessity of oncologic thyroid resections irrespective of the cytology result. Other genetic alterations are associated with thyroid malignancy with varying frequency and achieve less impact on the clinical management. Conclusion: Molecular genetic analysis of FNABs is increasingly performed in Germany. Standardization, quality controls, and validation of various methods need to be implemented in the near future to be able to compare the results. With increasing knowledge about the impact of genetic alterations on the prognosis of thyroid carcinomas, recommendations have to be defined that may lead to individually optimized treatment strategies.

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