scholarly journals Monogenic Causes of Strokes

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1855
Author(s):  
Justyna Chojdak-Łukasiewicz ◽  
Edyta Dziadkowiak ◽  
Sławomir Budrewicz
Keyword(s):  
Autosomal Recessive ◽  
Genetic Factors ◽  
Autosomal Dominant ◽  
Small Vessel Disease ◽  
Clinical Phenotype ◽  
Single Gene ◽  
Monogenic Disorders ◽  
Single Gene Disorders ◽  
Appropriate Therapy

Strokes are the main cause of death and long-term disability worldwide. A stroke is a heterogeneous multi-factorial condition, caused by a combination of environmental and genetic factors. Monogenic disorders account for about 1% to 5% of all stroke cases. The most common single-gene diseases connected with strokes are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) Fabry disease, mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS) and a lot of single-gene diseases associated particularly with cerebral small-vessel disease, such as COL4A1 syndrome, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). In this article the clinical phenotype for the most important single-gene disorders associated with strokes are presented. The monogenic causes of a stroke are rare, but early diagnosis is important in order to provide appropriate therapy when available.

scholarly journals Clinical case of myocardial infarction with unspecified familial hypercholesterolemia

2022 ◽  
Vol 17 (4) ◽  
pp. 74-78
Author(s):  
N. G. Lozhkina ◽  
A. N. Spiridonov
Keyword(s):  
Myocardial Infarction ◽  
Familial Hypercholesterolemia ◽  
Clinical Case ◽  
Autosomal Dominant ◽  
Clinical Symptoms ◽  
Cholesterol Metabolism ◽  
Single Gene ◽  
Low Density Lipoproteins ◽  
Dominant Disease ◽  
Appropriate Therapy

Familial hypercholesterolemia is a hereditary autosomal dominant disease characterized by a violation of cholesterol metabolism. This nosology was first described in the late 1930s by the Norwegian clinician Karl Moeller, he proposed the idea that hypercholesterolemia and tendon xanthomas are associated with cardiovascular diseases through the inheritance of a single gene. In 1964, two clinical phenotypes of familial hypercholesterolemia were discovered: heterozygous and homozygous, associated with an unfavorable prognosis. To date, it is known that the long-running process of accumulation of low-density lipoproteins in the intima of blood vessels may not have clinical symptoms for many years due to the developed system of collaterals and the absence of hemodynamically significant stenosis. However, without timely diagnosis and appropriate therapy, this condition inevitably leads to the development of a cardiovascular event. The article presents a clinical case demonstrating the development of myocardial infarction in a patient with a late diagnosis of this disease.

scholarly journals Primary atopic disorders

2018 ◽  
Vol 215 (4) ◽  
pp. 1009-1022 ◽  
Author(s):  
Jonathan J. Lyons ◽  
Joshua D. Milner
Keyword(s):  
Single Gene ◽  
Allergic Diseases ◽  
Therapeutic Benefit ◽  
Global Changes ◽  
Major Goal ◽  
Epithelial Barrier Function ◽  
Monogenic Disorders ◽  
Single Gene Disorders ◽  
Human Immunity ◽  
Novel Therapeutic Strategies

Monogenic disorders have provided fundamental insights into human immunity and the pathogenesis of allergic diseases. The pathways identified as critical in the development of atopy range from focal defects in immune cells and epithelial barrier function to global changes in metabolism. A major goal of studying heritable single-gene disorders that lead to severe clinical allergic diseases is to identify fundamental pathways leading to hypersensitivity that can be targeted to provide novel therapeutic strategies for patients with allergic diseases, syndromic and nonsyndromic alike. Here, we review known single-gene disorders leading to severe allergic phenotypes in humans, discuss how the revealed pathways fit within our current understanding of the atopic diathesis, and propose how some pathways might be targeted for therapeutic benefit.

Carrier testing for autosomal recessive disorders: a look at current practice in Germany

2021 ◽  
Vol 33 (1) ◽  
pp. 13-19
Author(s):  
Christian Netzer ◽  
Clara Velmans ◽  
Florian Erger ◽  
Julia Schreml
Keyword(s):  
Autosomal Recessive ◽  
Current Practice ◽  
Human Genetics ◽  
Single Gene ◽  
Recurrence Risk ◽  
Medical Practitioners ◽  
Autosomal Recessive Disorders ◽  
Monogenic Disorders ◽  
Acceptable Risks ◽  
Recessive Disorders

Abstract Counseling recurrence risks for monogenic disorders is one of the mainstays of human genetics. However, in practice, consultations concerning autosomal recessive disorders exceed the simple conveyance of a 25 % recurrence risk for future offspring. Medical geneticists should be aware of the multifaceted way in which autosomal recessive disorders can pose a diagnostic and counseling challenge in their daily lives and of the pitfalls they might encounter. Although the intentional or incidental detection of carrier states for autosomal recessive diseases happens more and more frequently, our current practice when clarifying their associated reproductive risks remains unsystematic and often subjectively guided. We question whether the approach of focusing on small recurrence risks for a single familial disease with extensive single-gene tests in the partner of a known carrier truly addresses the counseling needs of a couple seeking preconceptional genetic advice. Different perspectives between patients and medical practitioners (or between different medical practitioners) on “acceptable risks” or the extent to which such risks must be minimized raise the question of whether existing professional guidelines need to be clarified.

scholarly journals Hemoglobinopathies in Iran: An Updated Review

2020 ◽  
Author(s):  
Abolfazl Nasiri ◽  
Zohreh Rahimi ◽  
Asad Vaisi-Raygani
Keyword(s):  
Single Gene ◽  
Fetal Hemoglobin ◽  
World Population ◽  
Structural Variants ◽  
Molecular Defects ◽  
Monogenic Disorders ◽  
Single Gene Disorders ◽  
Hereditary Persistence ◽  
Specific Position ◽  
The Common

Hemoglobinopathies are the most common single gene disorders (monogenic disorders) in the world population.  Due to specific position of Iran and the presence of multi-ethnic groups in the country, there are many varieties in the molecular genetics and clinical features of hemoglobinopathies in Iran. Hemoglobinopathies include structural variants, thalassemias, and hereditary persistence of fetal hemoglobin. In this review, we look at the common structural variants in various parts of the country along with their hematological and clinical characteristics. Also, we discuss about the burden of the thalassemias in the country, different types, complications, molecular defects and therapy.

Monogenic forms of diabetes resulting from β‎ cell dysfunction

2011 ◽  
pp. 1754-1759
Author(s):  
Rachel Besser ◽  
Andrew Hattersley
Keyword(s):  
Clinical Phenotype ◽  
Single Gene ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Maturity Onset Diabetes ◽  
Monogenic Disorders ◽  
Cell Dysfunction ◽  
Onset Diabetes ◽  
Monogenic Forms Of Diabetes ◽  
Clinical Category

Monogenic diabetes refers to diabetes resulting from mutations in a single gene. This chapter discusses monogenic disorders causing β‎ cell dysfunction, which accounts for the majority of cases of monogenic diabetes. Patients can usually be divided into three clinical categories: maturity-onset diabetes of the young (MODY), which is dominantly inherited familial diabetes; neonatal diabetes, diagnosed under the age of 6 months; and monogenic diabetes syndromes, which are characterized by multiple nonpancreatic features. In each clinical category, there are several aetiological genes that usually result in a discrete clinical phenotype.

scholarly journals ABCB6 Polymorphisms are not Overly Represented in Patients with Porphyria

2021 ◽  
Author(s):  
Colin P Farrell ◽  
Gaël Nicolas ◽  
Robert J. Desnick ◽  
Charles J. Parker ◽  
Jerome Lamoril ◽  
...  
Keyword(s):  
Biosynthetic Pathway ◽  
Genetic Factors ◽  
Autosomal Dominant ◽  
Clinical Phenotype ◽  
Acute Intermittent Porphyria ◽  
Mendelian Inheritance ◽  
Erythropoietic Protoporphyria ◽  
Transporter Protein ◽  
Hereditary Coproporphyria ◽  
Knockout Animals

The Mendelian inheritance pattern of acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria is autosomal dominant, but the clinical phenotype is heterogeneous. Within the general population, penetrance is low, but among first-degree relatives of a symptomatic proband, penetrance is higher. These observations suggest that genetic factors, in addition to mutation of the specific enzyme of the biosynthetic pathway of heme, contribute to the clinical phenotype. Recent studies by others suggested that the genotype of the transporter protein ABCB6 contribute to the porphyria phenotype. Identifying the molecule(s) that are transported by ABCB6 has been problematic and has led to uncertainty with respect to how or if variants/mutants contribute to phenotypic heterogeneity. Knockout mouse models of Abcb6 have not provided a direction for investigation as homozygous knockout animals do not have a discrete phenotype. To address the proposed link between ABC6 genotype and porphyria phenotype, a large cohort of patients with acute hepatic porphyria and erythropoietic protoporphyria was analyzed. Our studies showed that ABCB6 genotype did not correlate with disease severity. Therefore, genotyping of ABCB6 in patients with acute hepatic porphyria and erythropoietic protoporphyria is not warranted.

scholarly journals Noninvasive prenatal exome sequencing inefficient for detecting single-gene disorders -- problems and possible solutions

2020 ◽  
Author(s):  
Dayne Filer ◽  
Piotr A Mieczkowski ◽  
Alicia Brandt ◽  
Kelly L Gilmore ◽  
Bradford C Powell ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Genetic Disease ◽  
Copy Number ◽  
Autosomal Dominant ◽  
Diagnostic Yield ◽  
Single Gene ◽  
Normal Karyotype ◽  
Noninvasive Testing ◽  
Single Gene Disorders ◽  
Structural Abnormalities

What's already known about this topic? (1) Sequencing-based noninvasive testing can detect large copy number abnormalities and some autosomal dominant single-gene disorders; (2) Exome sequencing (ES) on fetal samples provides 20% diagnostic yield for structural abnormalities after normal karyotype & microarray. What does this study add? (1) ES on cell-free DNA in three gravid patients with suspected genetic disease in the fetus; (2) We demonstrate broad sequencing approaches are limited by sampling and technical difficulties, concluding broad sequencing is currently inappropriate for noninvasive testing.

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