Autosomal Dominant Inheritance Flashcards
This is a condition where cholesterol deposits under the surface of the skin.
xanthomata
T/F. In autosomal dominant inheritance, males are affected in disproportionately higher incidence than female.
False. Approximately equal numbers
T/F. In autosomal dominant inheritance, persons are affected in each generation and males can transmit the condition to males or females and vice versa.
True.
This condition is due to a single mutant gene on the short arm of chromosome 19, and is inherited in an autosomal dominant fashion.
familial hypercholesterolaemia (FH)
T/F. If a heterozygous person affected by an autosomal dominant disease marries another person who is normal for that disease, then the chance of their offspring being affected is 50%.
True.
T/F. Although each affected individual has the same mutant gene, there is variation in the time of onset and severity of xanthomata and vascular disease.
True
Variable expression or variable expressivity is typical of an autosomal dominant trait. Its basis is unclear, but it is likely to be at least partly due to the effects of other ___ genes.
modifier
The gene for familial hypercholesterolaemia produces a protein that acts as a receptor for ___ in circulating low - density - lipoprotein (LDL) particles. These particles, which contain cholesterol, can be bound and then internalized by a wide variety of cells, via ____.
apolipoprotein B; clathrin -mediated endocytosis
T/F. Defects in this LDL receptor (LDLR) result in defective clearance and hence elevated levels of LDL – cholesterol.
True.
Mutations in the gene that encodes ____ are a rare cause of severe hypercholesterolaemia, while a less severe phenotype (type B hypercholesterolaemia) results from mutation of the gene that encodes the ____.
proprotein convertase subtilisin/kexin type 9 (PCSK9); apolipoprotein B - 100 protein (APOB)
Familial hypercholesterolaemia affects ___ individuals.
1 in 500
In marriages between affected heterozygotes for FH, what is the genotypic ratios?
one quarter is homozygous unaffected; one half heterozygous affected; one quarter homozygous affected
T/F. In the homozygous affected persons, there are no normal LDLRs & the disease shows precocious onset & increased severity w/ symptoms of coronary heart disease in late childhood.
True.
Family members at risk of familial hypercholesterolaemia can be counselled on the basis of ____, _____, or by tracking the defective gene within a family using ____.
plasma lipid profiles; mutation analysis; DNA analysis
In this autosomal dominant condition, heart muscle enlargement occurs, outflow obstruction is noted and a decrease in cardiac chamber size is seen, leading to a reduced ability to pump blood effectively.
hypertrophic cardiomyopathy (HCM)
Cholesterol-lowering therapy which work by competitively inhibiting HMG - CoA reductase, an enzyme involved in cholesterol synthesis
statins
Cholesterol-lowering therapy that works by inhibiting intestinal absorption of cholesterol.
ezetimibe
T/F. In contrast to hypertrophic cardiomyopathy, only 30% of dilated cardiomyopathy is familial and in these cases, mitochondrial and sarcomeric abnormalities in addition to muscular dystrophies are noted.
True.
Familial cardiomyopathy is a result of a mutation in one of the genes that encode ____ proteins. Approximately 80% of the mutations reside within just two of these genes: ____ and ____.
sarcoplasmic proteins; β - myosin heavy chain
(MYH7); myosin binding protein C (MYBPC3)
For familial hypertrophic cardiomyopathy, the penetrance varies among families from ____, with the clinical manifestations ranging from ____ to sudden ____.
25 to 100%; progressive heart failure; cardiac death
Those relatives who are at risk of hypertrophic cardiomyopathy can be offered cardiac screening, including ____ and ____ and, if affected, can be treated pharmacologically or surgically including, if there is a high risk of cardiac arrest, the insertion of an implantable ____.
electrocardiography; echocardiography; cardioverter - defibrillator or ICD
At least ____ autosomal dominant traits are known in humans.
4458
T/F. In general, autosomal dominant disorders tend to be less severe than recessive traits, and, whereas recessive traits usually result in defective enzymes, in dominant conditions, structural, carrier, receptor or tumour-suppressor proteins are usually altered.
True.
In many dominant traits, such as the form of inherited colon cancer known as ____ (FAP), an individual may have the mutant gene and yet have a normal phenotype. This is called ____.
familial adenomatous polyposis; non-penetrance
T/F. Non-penetrance produces skipped generation which is uncharacteristical of autosomal dominant traits.
True.
T/F.The onset of some dominant traits is age-dependent and reassurance of family members at risk on the basis of clinical examination is not possible until they reach an advanced age.
True. for example Huntington disease
When a condition shows full penetrance, such as ____, the recurrence risk for the clinically normal parents of an affected child is low but not negligible because of _____.
achondroplasia; gonadal mosaicism
T/F. The presence of dominant mutations confined to the gonad (gonadal mosaicism) would cause a high recurrence risk and can only be proven when unaffected parents have a second affected child.
True. In this case, the parents are clinically normal because the mutation is confined to the germ cells.
____ is a common adult - onset form of muscular dystrophy that is due to an unstable length mutation.
Myotonic dystrophy
T/F. In myotonic dystrophy, small length mutations may produce few or no symptoms, but expansion in successive generations can result in increasing disease severity.
True.
T/F. For several autosomal dominant traits, including Apert syndrome, progressive myositis ossificans, Marfan syndrome and achondroplasia, the risk of a new mutation increases with increasing paternal age, and for some dominant traits like retinoblastoma and neurofibromatosis, DNA analysis has demonstrated a paternal excess of new mutations.
True.
