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Copyright of Cukurova Medical Journal / Çukurova Üniversitesi Tip Fakültesi Dergisi is the property of Cukurova University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Multiple idiopathic cervical root resorption (MICRR) is a disease with an unknown etiology that causes invasive cervical root resorption in multiple teeth. Although previous MICRR genomic studies have identified candidate gene variants, the etiology of the condition remains poorly understood. In the present study, we investigated the genetic causality of MICRR to explore candidate variants. Saliva samples from a family containing 2 affected and two unaffected subjects with the dominant transmission of MICRR were subjected to whole-exome sequencing. As a result, we identified novel candidate variants of 10 genes. Each variant was confirmed by Sanger sequencing. Among them, the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines classified doublecortin domain containing 1 (c.1099 C > T) and β-defensin 114 (c.189 T > G) as "pathogenic," and solute carrier family 45 member 2 (c.152_153del) as "likely pathogenic." These results provide new insight to help clarify the pathogenesis of MICRR, and the variants could be applied for further investigation to understand invasive cervical root resorption. [ABSTRACT FROM AUTHOR]

Early onset ataxia (EOA) concerns a heterogeneous disease group, often presenting with other comorbid phenotypes such as myoclonus and epilepsy. Due to genetic and phenotypic heterogeneity, it can be difficult to identify the underlying gene defect from the clinical symptoms. The pathological mechanisms underlying comorbid EOA phenotypes remain largely unknown. The aim of this study is to investigate the key pathological mechanisms in EOA with myoclonus and/or epilepsy. For 154 EOA-genes we investigated (1) the associated phenotype (2) reported anatomical neuroimaging abnormalities, and (3) functionally enriched biological pathways through in silico analysis. We assessed the validity of our in silico results by outcome comparison to a clinical EOA-cohort (80 patients, 31 genes). EOA associated gene mutations cause a spectrum of disorders, including myoclonic and epileptic phenotypes. Cerebellar imaging abnormalities were observed in 73–86% (cohort and in silico respectively) of EOA-genes independently of phenotypic comorbidity. EOA phenotypes with comorbid myoclonus and myoclonus/epilepsy were specifically associated with abnormalities in the cerebello-thalamo-cortical network. EOA, myoclonus and epilepsy genes shared enriched pathways involved in neurotransmission and neurodevelopment both in the in silico and clinical genes. EOA gene subgroups with myoclonus and epilepsy showed specific enrichment for lysosomal and lipid processes. The investigated EOA phenotypes revealed predominantly cerebellar abnormalities, with thalamo-cortical abnormalities in the mixed phenotypes, suggesting anatomical network involvement in EOA pathogenesis. The studied phenotypes exhibit a shared biomolecular pathogenesis, with some specific phenotype-dependent pathways. Mutations in EOA, epilepsy and myoclonus associated genes can all cause heterogeneous ataxia phenotypes, which supports exome sequencing with a movement disorder panel over conventional single gene panel testing in the clinical setting. • EOA associated gene mutations cause a spectrum of disorders, including myoclonic and epileptic phenotypes. • Cerebello-thalamo-cortical network involvement might contribute to the etiological heterogeneity of EOA phenotypes. • Metabolic lysosomal and lipid pathways are overrepresented in ataxia with comorbid myoclonus. • Due to overlapping molecular pathogenesis, exome sequencing with a full movement disorder panel is advised in pediatric ataxia. [ABSTRACT FROM AUTHOR]

Copyright of Dynamis is the property of Dynamis - Facultad de Medicina de la Universidad de Granada and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Advances in genetic and genomic knowledge have revolutionized the diagnosis, management, treatment, and prevention of genetic disorders. Genetic counselors interpret and explain genomic information to patients, order the right genetic/genomic tests, calculate genetic risks, explain inheritance patterns, interpret genomic variants, and subsequently handle psychosocial and ethical issues raised within the individuals/families. Genetic counseling is a major part of the modern integrated modern genomic medicine academic and health-care unit. This review provides factual information on the principles and practices of genetic counseling. [ABSTRACT FROM AUTHOR]

Human genome variation has increasingly posed challenges and opportunities for patients, medical providers, and an increasing group of stakeholders including advocacy groups, disadvantaged communities, public health experts, and scientists. Here, advances in genomic sequencing and mapping technologies are discussed with particular attention to the increasing ability to detect personal and population genome variation and the potential for accurate integration of variation into health and disease-related care. Genome mapping, one technique used to create genome map scaffolds, has now been combined with long read sequencing. New technologies have led to improved variation detection, including cryptic structural variation and diverse variants with different degrees of disease association. Combined with advances in automated and medical interpretations, variation detection is increasingly being applied in healthcare. These advances promise to make disease diagnostics more rapid, and potentially more accessible, to those with medical needs. Consequentially, the need for medical genetics and genomics experts is increasing. Here, the opportunities and potential challenges for application of genome-scale variation detection in disease are examined. (<300 words). [ABSTRACT FROM AUTHOR]

Objective: To evaluate Mendelian causes of neurodegenerative disorders in a cohort of pediatric patients.Study Design: Patients enrolled in the Center for Applied Genomics Biobank at the Children's Hospital of Philadelphia with neurodegenerative symptoms were identified using an algorithm that consisted of including and excluding selected International Classification of Diseases, 9th and 10th edition codes. A manual chart review was then performed to abstract detailed clinical information.Results: Of approximately 100 000 patients enrolled in the Center for Applied Genomics Biobank, 76 had a neurodegenerative phenotype. After chart review, 7 patients were excluded. Of the remaining 69 patients, 42 had a genetic diagnosis (60.9%) and 27 were undiagnosed (39.1%). There were 32 unique disorders. Common diagnoses included Rett syndrome, mitochondrial disorders, and neuronal ceroid lipofuscinoses.Conclusions: The disorders encountered in our cohort demonstrate the diverse diseases and pathophysiology that contribute to pediatric neurodegeneration. Establishing a diagnosis often informed clinical management, although curative treatment options are lacking. Many patients who underwent genetic evaluation remained undiagnosed, highlighting the importance of continued research efforts in this field. [ABSTRACT FROM AUTHOR]

Since the human genome was first sequenced in 2003, millions of consumers and medical professionals have swarmed the field of medical genetics, seeking to peer into the crystal ball and see what their own, or their patients', futures may hold. Also rushing in are direct-toconsumer genetic testing companies like 23andMe and AncestryDNA, which can circumvent medical privacy laws by offering genetic testing without a medical provider. Medical privacy regulations, such as the Health Information Portability and Accountability Act of 1996 (HIPAA), the Genetic Information Discrimination Act of 2008 (GINA), and those promulgated by the Federal Trade Commission, do not regulate these companies adequately for a litany of reasons. These loopholes and shortcomings in regulation leave American consumers substantially less protected, less medically informed, and in some instances can jeopardize national security. This Note proposes that Congress should enact legislation overhauling the current regulatory regime in at least three ways: (1) the "covered entity" approach should be abandoned and replaced with a data-driven model; (2) the Safe Harbor provision of HIPAA should explicitly exclude genomic data; and (3) consumers should be given a "right to be forgotten" and compel companies to delete their data. These reforms would significantly strengthen consumers' genetic privacy and give them an escape hatch to safeguard the core of their identity. [ABSTRACT FROM AUTHOR]

Copyright of Dynamis is the property of Dynamis - Facultad de Medicina de la Universidad de Granada and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Treaties & Documents / Razprave in Gradivo is the property of Institut za Narodnostna Vprasanja and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This document is a corrigendum to an article titled "Defining the molecular pathology and consequent phenotypes in Egyptian HB patients" published in the Journal of Genetic Engineering & Biotechnology. The authors acknowledge errors in the original article, including the inclusion of the word "biallelic" which will be deleted, and the incorrect spelling of "homozygous" in four places, which should be "hemizygous." The corrigendum provides the DOI of the original article and a link to access it. [Extracted from the article]

Background and objectives: The occurrence and development of lung cancer are closely linked to epigenetic modification. Abnormal DNA methylation in the CpG island region of genes has been found in many cancers. Protein kinase C delta binding protein (PRKCDBP) is a potential tumor suppressor and its epigenetic changes are found in many human malignancies. This study investigated the possibility of PRKCDBP methylation as a potential biomarker for non-small cell lung cancer (NSCLC). Methods: We measured the methylation levels of PRKCDBP in the three groups of NSCLC tissues. Promoter activity was measured by the dual luciferase assay, with 5'-aza-deoxycytidine to examine the effect of demethylation on the expression level of PRKCDBP. Results: The methylation levels of PRKCDBP in tumor tissues and 3 cm para-tumor were higher than those of distant (>10 cm) non-tumor tissues. Receiver operating characteristic (ROC) curve analysis between tumor tissues and distant non-tumor tissues showed that the area under the line (AUC) was 0.717. Dual luciferase experiment confirmed that the promoter region was able to promote gene expression. Meanwhile, in vitro methylation of the fragment (PRKCDBP_Me) could significantly reduce the promoter activity of the fragment. Demethylation of 5'-aza-deoxycytidine in lung cancer cell lines A549 and H1299 showed a significant up-regulation of PRKCDBP mRNA levels. Conclusion: PRKCDBP methylation is a potential and promising candidate biomarker for non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Background: Autoinflammatory disorders are the group of inherited inflammatory disorders caused due to the genetic defect in the genes that regulates innate immune systems. These have been clinically characterized based on the duration and occurrence of unprovoked fever, skin rash, and patient's ancestry. There are several autoinflammatory disorders that are found to be prevalent in a specific population and whose disease genetic epidemiology within the population has been well understood. However, India has a limited number of genetic studies reported for autoinflammatory disorders till date. The whole genome sequencing and analysis of 1029 Indian individuals performed under the IndiGen project persuaded us to perform the genetic epidemiology of the autoinflammatory disorders in India. Results: We have systematically annotated the genetic variants of 56 genes implicated in autoinflammatory disorder. These genetic variants were reclassified into five categories (i.e., pathogenic, likely pathogenic, benign, likely benign, and variant of uncertain significance (VUS)) according to the American College of Medical Genetics and Association of Molecular pathology (ACMG-AMP) guidelines. Our analysis revealed 20 pathogenic and likely pathogenic variants with significant differences in the allele frequency compared with the global population. We also found six causal founder variants in the IndiGen dataset belonging to different ancestry. We have performed haplotype prediction analysis for founder mutations haplotype that reveals the admixture of the South Asian population with other populations. The cumulative carrier frequency of the autoinflammatory disorder in India was found to be 3.5% which is much higher than reported. Conclusion: With such frequency in the Indian population, there is a great need for awareness among clinicians as well as the general public regarding the autoinflammatory disorder. To the best of our knowledge, this is the first and most comprehensive population scale genetic epidemiological study being reported from India. [ABSTRACT FROM AUTHOR]

Dravet syndrome is a severe developmental and epileptic encephalopathy characterized by the onset of prolonged febrile and afebrile seizures in infancy and SCN1A gene mutations. In some cases, non- SCN1A gene mutations can present with a phenotype very similar to that of Dravet syndrome. The aim of this study was to compare phenotypes of patients with SCN1A and non- SCN1A gene mutation-related Dravet syndrome. Thirty-six patients with Dravet syndrome-like phenotypes were followed from July 2017 to December 2019. We retrospectively analyzed their clinical profiles and genetic surveys. Of the 36 enrolled patients, 15 (41.7%) had SCN1A mutations, one (2.8%) had an SCN8A mutation, one (2.8%) had an STX1B mutation, and five females (13.9%) had PCDH 19 mutations. The median age at first seizure onset was 7 months in those with SCN1A mutations, 1.3 years in those with PCDH19 mutations, and 10 months for the remaining patients. The majority of the patients with SCN1A mutations had status epilepticus (80% vs. 20%) and fever-sensitive seizures (76% vs. 31%) compared to those with PCDH19 mutations. The patients with SCN1A -related seizures had a higher rate of focal seizures as first seizure type than those without SCN1A mutations. Three of five (60%) patients with PCDH19 mutations had brain magnetic resonance imaging abnormalities. The three most commonly used antiseizure medications were sodium valproate, levetiracetam, and clobazam. Seven of the 15 patients with SCN1A mutations used stiripentol. The median time from seizure onset to genetic diagnosis was 6.6 years (range 4 months–22.3 years). The patients with SCN1A mutations in this study had high rates of fever-sensitive seizures, status epilepticus, seizure onset with focal seizure type, and relatively young age at seizure onset. The patients with PCDH19 mutations had a relatively high rate of abnormal brain magnetic resonance imaging findings. [ABSTRACT FROM AUTHOR]

Over the last 50 years, there have been major advances in knowledge and technology regarding genetic diseases, and the subsequent ability to control them in a cost-effective manner. This review traces these advances through research into genetic diseases of animals at Massey University (Palmerston North, NZ), and briefly discusses the disorders investigated during that time, with additional detail for disorders of major importance such as bovine α-mannosidosis, ovine ceroid-lipofuscinosis, canine mucopolysaccharidosis IIIA and feline hyperchylomicronaemia. The overall research has made a significant contribution to veterinary medicine, has provided new biological knowledge and advanced our understanding of similar disorders in human patients, including testing various specific therapies prior to human clinical trials. [ABSTRACT FROM AUTHOR]

Objective: to discuss strategic challenges in complex health organizations sustained by an analysis in a Medical Genetics Center at a National Health Research Institute in Brazil. Method: Démarche Stratégique adapted for use with research institutes, including the policy formulation function. The study used institution’s databases and workshops with key actors between Dec/2014 and Jun/2015. Results: Were defined the segments: clinical diagnosis, lysosomal diseases, osteogenesis imperfecta, genetic counseling, cytogenetics, biochemistry, and genomics. The findings reveal that the segments are aligned with the Institute’s mission when it comes to referral care, although investment is required in strategic areas. The clinical diagnosis, lysosomal diseases, and genomics segments stood out in the scientific output portfolio. The findings show that progress needs to be made with policy implementation and planning to improve access to new technologies, together with investment in training and development, and the strengthening of coordination and collaboration between research institutes and referral services and between the wider healthcare network and research, care, and teaching. The inclusion of the policy formulation dimension was essential to highlight the unique role medical genetics plays in Brazil’s public health system and the importance of developing action plans in the field of public health. [ABSTRACT FROM AUTHOR]

Rare genetic diseases are an important public health problem, but they are still little studied in Collective Health. This article aims to analyze the 'therapeutic itineraries' of patients in search of a diagnosis and treatment for rare genetic diseases in the cities of Rio de Janeiro, Salvador and Porto Alegre. It focuses on the material challenges, emotional and structural problems faced in these trajectories. Semi-structured interviews were conducted with patients/caregivers and health professionals in the context of public health medical genetics. Our findings suggest that the experience of the rare genetic disease is aggravated by practical, inter-relational and bureaucratic/institutional problems. The reality of long and circuitous journeys to obtain a diagnosis, non-geneticists' lack of knowledge about rare diseases, difficulties in transportation and access to specialists, diagnostic and complementary examinations, and access to high-cost medicines and food supplies were common challenges in all the narratives examined in the three Brazilian cities. In addition, adherence to care provided by medical genetics requires action and strategies that depend on arrangements involving family members, physicians, patient associations, and the state. [ABSTRACT FROM AUTHOR]

Some genetic disorders are associated with recurrent inflammation of the oral mucosa and with periodontal disease. Of the various incarnations of glycogen-storage diseases (GSD), type Ib is such a disorder. It is caused by a lack of polymorphous nuclear neutrophilic granulocytes (PMN) and PMN dysfunction. The present case report relates to a patient suffering from GSD type Ib and describes the oral findings between the ages of seven and 19 years. His oral situation was characterized by frequent ulcerations in various regions of the oral mucosa, persistent gingivitis, and advanced periodontal disease, initially affecting the deciduous molars (F3 furcation involvement). A comprehensive preventive dental-care program and excellent compliance on the part of the patient could not prevent periodontal destruction of the mandibular right first permanent molar (4 mm attachment loss, F2 furcation involvement). [ABSTRACT FROM AUTHOR]

Understanding the principles of basic genetics is the beginning of understanding more complex and advanced genetic studies, such as epigenetics. This article presents a review of the basic concepts of genetics, Mendelian and non-Mendelian patterns of inheritance, and basic genetic testing. [ABSTRACT FROM AUTHOR]

The author reflects on pivotal communications challenges of genetic testing, diagnosis and counseling and genetic technologies are developed and the volume and complexity of available genetic information increases, new skills and strategies for service delivery will need to be developed. It also mentions influence on current practice, strategies for genetic counseling and results disclosure, and the many challenges for sharing genetic information to improve health care and decision making.

Copyright of Cukurova Medical Journal / Çukurova Üniversitesi Tip Fakültesi Dergisi is the property of Cukurova University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)