Role of Amniocentesis in the Intrauterine Detection of Genetic Disorders

Background: Cervical internal carotid artery (ICA) tortuosity has been associated with vascular risk and stroke as well as genetic disorders related to abnormal extracellular matrix remodeling. It is plausible that dystrophic or aberrant arterial remodeling may therefore relate to cervical ICA tortuosity. We hypothesized that cervical ICA tortuosity relates to carotid dilatation, but not to traditional ultrasound (US) markers of atherosclerosis. Methods: Subjects of the NOMAS with available time-of-flight MRA were included in our study. Cervical ICA tortuosity was defined as a bend in the distal cervical ICA of > 90° as seen on MRA. We excluded subjects with < 5 cm of the cervical ICA visualized. Distensibility was calculated as the percentage excursion of the right CCA diastolic diameter during systole, which was assessed by high-resolution B-mode US of the right common carotid artery (CCA). We used multivariable logistic regression analyses to estimate odds ratios for the association of cervical ICA tortuosity and Doppler measures of carotid wall aging. Results: We visualized cervical ICA tortuosity in 468 NOMAS participants (mean age 64±8 years, 70% women, 70% Hispanic). It was present in 23% of subjects. In unadjusted models, cervical ICA tortuosity was more common in women (OR 2.34, 95% CI 1.34-4.11), Hispanics (OR 1.85, 95%CI 1.06-3.25) and those with higher diastolic blood pressures (OR per mm Hg 1.04, 95%CI 1.01-1.06), and less common among smokers (OR 0.23, 95%CI 0.07-0.78). In models adjusted for demographic and vascular risks, right CCA tortuosity was associated with ipsilateral larger CCA DD (OR 1.42, 95%CI 1.02-1.96) and borderline associated with lower distensibility (OR 0.94, 95%CI 0.87-1.01, P=0.06) but not with ipsilateral ICA IMT (OR 0.26, 95%CI 0.14-4.77), number of plaques (OR 1.08, 95%CI 0.76-1.53), maximum plaque thickness (OR 0.96, 95%CI 0.73-1.27), or plaque area (1.00, 95%CI 0.97-1.05). Conclusions: Cervical ICA tortuosity associates with ipsilateral cervical ICA dilatation and lower distensibility, but not with traditional US markers of atherosclerosis. The association with diastolic blood pressure suggests a role of steady, rather than pulsatile, hemodynamics in aberrant cervical ICA remodeling.

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Genetic Disorders, Genotyping Techniques and the Emerging Role of Tetra-ARMS-PCR as a Diagnostic Tool

Resonance ◽

10.1007/s12045-021-1225-x ◽

2021 ◽

Vol 26 (9) ◽

pp. 1229-1240

Author(s):

Motiur Rahaman ◽

Mandrita Mukherjee ◽

Nishant Chakravorty

Keyword(s):

Diagnostic Tool ◽

Genetic Disorders ◽

Arms Pcr

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Reaching Future Scientists, Consumers, & Citizens

The American Biology Teacher ◽

10.1525/abt.2014.76.6.5 ◽

2014 ◽

Vol 76 (6) ◽

pp. 379-383 ◽

Cited By ~ 3

Author(s):

Melissa A. Hicks ◽

Rebecca J. Cline ◽

Angela M. Trepanier

Keyword(s):

Personalized Medicine ◽

Genetic Basis ◽

Genetic Disorders ◽

Single Gene ◽

Personal Health ◽

Adult Onset ◽

Biology Textbooks ◽

Multifactorial Diseases ◽

Single Gene Disorders

An understanding of how genomics information, including information about risk for common, multifactorial disease, can be used to promote personal health (personalized medicine) is becoming increasingly important for the American public. We undertook a quantitative content analysis of commonly used high school textbooks to assess how frequently the genetic basis of common multifactorial diseases was discussed compared with the “classic” chromosomal–single gene disorders historically used to teach the concepts of genetics and heredity. We also analyzed the types of conditions or traits that were discussed. We identified 3957 sentences across 11 textbooks that addressed multifactorial and “classic” genetic disorders. “Classic” gene disorders were discussed relatively more frequently than multifactorial diseases, as was their genetic basis, even after we enriched the sample to include five adult-onset conditions common in the general population. Discussions of the genetic or hereditary components of multifactorial diseases were limited, as were discussions of the environmental components of these conditions. Adult-onset multifactorial diseases are far more common in the population than chromosomal or single-gene disorders; many are potentially preventable or modifiable. As such, they are targets for personalized medical approaches. The limited discussion in biology textbooks of the genetic basis of multifactorial conditions and the role of environment in modifying genetic risk may limit the public’s understanding and use of personalized medicine.

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ROLE OF GENETIC POLYMORPHISMS ASSOCIATED WITH THROMBOPHILIA, PROTHROMBOTIC STATE AND FOLATE CYCLE DISTURBANCES IN WOMEN WITH REPRODUCTIVE DISORDERS

Тромбоз, гемостаз и реология ◽

10.25555/thr.2017.2.0784 ◽

2017 ◽

Author(s):

А. Киселева ◽

Е. Бутина ◽

Г. Зайцева ◽

Е. Попонина ◽

С. Игнатьев ◽

...

Keyword(s):

Genetic Disorders ◽

Folate Metabolism ◽

Clear Understanding ◽

Reproductive Disorders ◽

Primary Infertility ◽

Risk Alleles ◽

Heterozygous Form ◽

Folate Cycle ◽

Pai 1

Введение. Причины осложнения беременности достаточно многообразны: хромосомные и генетические нарушения, эндокринопатии, анатомические, инфекционные, иммунные и тромбофилические факторы. До настоящего времени нет четкого представления об истинных составляющих нарушения гестационного процесса. Материалы и методы. Проведено исследование аллелей, ассоциированных с тромбофилией и протромботическими состояниями, у 629 женщин и генов фолатного обмена у 277 женщин с отягощенным акушерским анамнезом. Результаты. Проанализирован характер распределения «аллелей риска» у женщин с первичным бесплодием, осложненными родами, неразвивающимися беременностями и у женщин без отягощенного акушерского анамнеза. Представлены данные о частоте встречаемости генетических мутаций, ассоциированных с тромбофилией (F2, F5), протромботическими состояниями (F7, F13, FGB, ITGA-2, ITGB-3, PAI-1) и нарушениями фолатного обмена (MTFFR, MTR, MTRR) у женщин с репродуктивными расстройствами. Заключение. Обнаружены статистически значимые различия в частоте распределения гетерозиготной формы полиморфизма ITGB3 у женщин с первичным бесплодием и осложненными родами в сравнении с женщинами без репродуктивных неудач. Влияние других полиморфных генов, ассоциированных с тромбофилией, протромботическими состояниями и нарушениями фолатного обмена, на наступление, течение и исход беременности не подтверждено. Introduction. The causes of pregnancy complications are quite multiformous: chromosomal and genetic disorders, endocrinopathies, anatomical, infectious, immune and thrombophilic factors. Until now there is no clear understanding of true components of gestational disorders. Materials and methods. We studied alleles associated with thrombophilia and prothrombotic conditions (in 629 women) and folate metabolism genes (in 277 women) with burdened obstetrical anamnesis. Results. The distribution of «risk alleles» in women with primary infertility, complicated delivery, non-developing pregnancy and at women without aggravated obstetric history was analyzed. Data about incidence of genetic mutations associated with thrombophilia (F2, F5), prothrombotic states (F7, F13, FGB, ITGA-2, ITGB-3, PAI-1) and folate metabolism disturbances (MTFFR, MTR, MTRR) in women with reproductive disorders are presented. Conclusion. Statistically signifi cant diff erences in distribution rate of heterozygous form of ITGB3 polymorphism in women with primary infertility and complicated delivery in comparison with women without reproductive failures were found. Impact of other polymorphic genes associated with thrombophilia, prothrombotic states and disturbances of folate metabolism to onset, gestation course and outcome of pregnancy was not proved.

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Chronic heart failure diagnosis: genetics

ESC CardioMed ◽

10.1093/med/9780198784906.003.0410 ◽

2018 ◽

pp. 1781-1787

Author(s):

Perry Elliott

Keyword(s):

Heart Failure ◽

Genetic Disorders ◽

Fluid Retention ◽

Response To Therapy ◽

The Body ◽

Clinical Approach ◽

Functional Abnormality ◽

Artery Disease ◽

Heart Failure Diagnosis

Heart failure refers to a state in which the cardiac output, no longer compensated by endogenous mechanisms, fails to meet the metabolic demands of the body. Clinically, it is defined by symptoms of breathlessness, fatigue, fluid retention, and a cardiac structural or functional abnormality. Most cases of heart failure are caused by coronary artery disease, hypertension, diabetes, and valvular heart disease, but the risk of heart failure also depends on genetic predisposition for the causative disorder as well as genetic variation that modulates the maladaptive pathophysiological response to pathophysiological stressors and the response to therapy. In a small, but almost certainly underdiagnosed proportion of cases, heart failure is caused by Mendelian genetic disorders of heart muscle (cardiomyopathies) that are mostly inherited as autosomal dominant traits characterized by locus and allelic heterogeneity and highly variable clinical expression. This chapter briefly reviews the clinical approach to the diagnosis of genetic disorders that cause heart failure and the role of genetic testing in everyday practice.

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Trimethyllysine: From Carnitine Biosynthesis to Epigenetics

International Journal of Molecular Sciences ◽

10.3390/ijms21249451 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9451

Author(s):

Marijn N. Maas ◽

Jordi C. J. Hintzen ◽

Miriam R. B. Porzberg ◽

Jasmin Mecinović

Keyword(s):

Protein Function ◽

Genetic Disorders ◽

Enzymatic Reactions ◽

Lysine Methylation ◽

Nucleosome Assembly ◽

Cellular Processes ◽

Subsequent Effect ◽

Control Protein ◽

Epigenetic Processes

Trimethyllysine is an important post-translationally modified amino acid with functions in the carnitine biosynthesis and regulation of key epigenetic processes. Protein lysine methyltransferases and demethylases dynamically control protein lysine methylation, with each state of methylation changing the biophysical properties of lysine and the subsequent effect on protein function, in particular histone proteins and their central role in epigenetics. Epigenetic reader domain proteins can distinguish between different lysine methylation states and initiate downstream cellular processes upon recognition. Dysregulation of protein methylation is linked to various diseases, including cancer, inflammation, and genetic disorders. In this review, we cover biomolecular studies on the role of trimethyllysine in carnitine biosynthesis, different enzymatic reactions involved in the synthesis and removal of trimethyllysine, trimethyllysine recognition by reader proteins, and the role of trimethyllysine on the nucleosome assembly.

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Molecular Pathogenesis and the Possible Role of Mitochondrial Heteroplasmy in Thoracic Aortic Aneurysm

Life ◽

10.3390/life11121395 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1395

Author(s):

A. V. Suslov ◽

M. A. Afanasyev ◽

P. A. Degtyarev ◽

P. V. Chumachenko ◽

M. Bagheri Ekta ◽

...

Keyword(s):

Aortic Aneurysm ◽

Thoracic Aortic Aneurysm ◽

Aortic Wall ◽

Morphological Changes ◽

Genetic Disorders ◽

Threatening Condition ◽

Mitochondrial Pathology ◽

Active Research ◽

Mitochondrial Dna Heteroplasmy

Thoracic aortic aneurysm (TAA) is a life-threatening condition associated with high mortality, in which the aortic wall is deformed due to congenital or age-associated pathological changes. The mechanisms of TAA development remain to be studied in detail, and are the subject of active research. In this review, we describe the morphological changes of the aortic wall in TAA. We outline the genetic disorders associated with aortic enlargement and discuss the potential role of mitochondrial pathology, in particular mitochondrial DNA heteroplasmy, in the disease pathogenesis.

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Maternal mosaicism for a missense variant in the SMS gene that causes Snyder-Robinson syndrome

Molecular Case Studies ◽

10.1101/mcs.a006122 ◽

2021 ◽

pp. mcs.a006122

Author(s):

Mohammad Marhabaie ◽

Scott E Hickey ◽

Katherine E Miller ◽

Olivia Grischow ◽

Kathleen M Schieffer ◽

...

Keyword(s):

High Throughput Sequencing ◽

De Novo ◽

Genetic Disorders ◽

Missense Variant ◽

Hyperinsulinemic Hypoglycemia ◽

Spermine Synthase ◽

Genetic Mosaicism ◽

The Family ◽

Bilateral Sensorineural Hearing Loss

There is increasing recognition for the contribution of genetic mosaicism to human disease, particularly as high-throughput sequencing has enabled detection of sequence variants at very low allele frequencies. Here, we describe an infant male who presented at 9 months of age with hypotonia, dysmorphic features, congenital heart disease, hyperinsulinemic hypoglycemia, hypothyroidism, and bilateral sensorineural hearing loss. Whole-genome sequencing of the proband and the parents uncovered an apparent de novo mutation in the X-linked SMS gene. SMS encodes spermine synthase, which catalyzes the production of spermine from spermidine. Inactivation of the SMS gene disrupts the spermidine/spermine ratio, resulting in Snyder-Robinson syndrome. The variant in our patient is absent from the gnomAD and ExAC databases and causes a missense change (p.Arg130Cys) predicted to be damaging by most in silico tools. While Sanger sequencing confirmed the de novo status in our proband, PCR and deep targeted resequencing to ~84,000-175,000x depth revealed that the variant is present in blood from the unaffected mother at ~3% variant allele frequency. Our findings thus provided a long-sought diagnosis for the family while highlighting the role of parental mosaicism in severe genetic disorders.

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The correction of epidermal barrier dysfunction in atopic dermatitis patients

Rossiiskii Allergologicheskii ZHurnal ◽

10.36691/rja386 ◽

2016 ◽

Vol 13 (3) ◽

pp. 59-64

Author(s):

O G Elisyutina ◽

O V Shtyrbul ◽

E N Zemskaya

Keyword(s):

Atopic Dermatitis ◽

Genetic Disorders ◽

Multifactorial Disease ◽

Complex Treatment ◽

Barrier Dysfunction ◽

Epidermal Barrier ◽

Endogenous Factors ◽

Leading Role ◽

Mechanisms Of Development

Atopic dermatitis is chronic inflammatory multifactorial disease, which has genetic disorders, immune mechanisms of development and is under the ainfluence of a combination of exogenous and endogenous factors. Recently a leading role of the epidermal barrier dysfunction in the pathogenesis of atopic dermatitis was shown. The article presents data about emollient for skin care efficacy - Cetaphil® RESTORADERM, which consists of preceramides and filaggrin breakdown products in complex treatment of atopic dermatitis patients.

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