Autosomal Dominant Inheritance

Question 1

This is a condition where cholesterol deposits under the surface of the skin.

Answer 1

xanthomata

Question 2

T/F. In autosomal dominant inheritance, males are affected in disproportionately higher incidence than female.

Answer 2

False. Approximately equal numbers

Question 3

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.

Answer 3

True.

Question 4

This condition is due to a single mutant gene on the short arm of chromosome 19, and is inherited in an autosomal dominant fashion.

Answer 4

familial hypercholesterolaemia (FH)

Question 5

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%.

Answer 5

True.

Question 6

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.

Answer 6

True

Question 7

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.

Answer 7

modifier

Question 7

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 ____.

Answer 7

apolipoprotein B; clathrin -mediated endocytosis

Question 8

T/F. Defects in this LDL receptor (LDLR) result in defective clearance and hence elevated levels of LDL – cholesterol.

Answer 8

True.

Question 9

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 ____.

Answer 9

proprotein convertase subtilisin/kexin type 9 (PCSK9); apolipoprotein B - 100 protein (APOB)

Question 10

Familial hypercholesterolaemia affects ___ individuals.

Answer 10

1 in 500

Question 11

In marriages between affected heterozygotes for FH, what is the genotypic ratios?

Answer 11

one quarter is homozygous unaffected; one half heterozygous affected; one quarter homozygous affected

Question 12

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.

Answer 12

True.

Question 13

Family members at risk of familial hypercholesterolaemia can be counselled on the basis of ____, _____, or by tracking the defective gene within a family using ____.

Answer 13

plasma lipid profiles; mutation analysis; DNA analysis

Question 14

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.

Answer 14

hypertrophic cardiomyopathy (HCM)

Question 14

Cholesterol-lowering therapy which work by competitively inhibiting HMG - CoA reductase, an enzyme involved in cholesterol synthesis

Answer 14

statins

Question 15

Cholesterol-lowering therapy that works by inhibiting intestinal absorption of cholesterol.

Answer 15

ezetimibe

Question 16

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.

Answer 16

True.

Question 16

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 ____.

Answer 16

sarcoplasmic proteins; β - myosin heavy chain
(MYH7); myosin binding protein C (MYBPC3)

Question 17

For familial hypertrophic cardiomyopathy, the penetrance varies among families from ____, with the clinical manifestations ranging from ____ to sudden ____.

Answer 17

25 to 100%; progressive heart failure; cardiac death

Question 18

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 ____.

Answer 18

electrocardiography; echocardiography; cardioverter - defibrillator or ICD

Question 19

At least ____ autosomal dominant traits are known in humans.

Answer 19

4458

Question 20

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.

Answer 20

True.

Question 21

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 ____.

Answer 21

familial adenomatous polyposis; non-penetrance

Question 22

T/F. Non-penetrance produces skipped generation which is uncharacteristical of autosomal dominant traits.

Answer 22

True.

Question 23

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.

Answer 23

True. for example Huntington disease

Question 24

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 _____.

Answer 24

achondroplasia; gonadal mosaicism

Question 25

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.

Answer 25

True. In this case, the parents are clinically normal because the mutation is confined to the germ cells.

Question 26

____ is a common adult - onset form of muscular dystrophy that is due to an unstable length mutation.

Answer 26

Myotonic dystrophy

Question 27

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.

Answer 27

True.

Question 28

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.

Answer 28

True.