Genetic Disorders and Terminology

Question 1

Familial hypercholerolemia

Mode of transmission, clinical features, name of gene

Answer 1

Autosomal DOMINANT
Deficiency of LDLR
-Example of haploinsufficiency
-Influenced by lifestyle factors

Question 2

Huntington’s Disease

Mode of transmission, clinical features, name of gene

Answer 2

Autosomal DOMINANT
Example of gain of function of the protein
-Triplet repeat expansion disorder, displays anticipation
High penetrance, 90% of cases are adult onset

Question 3

Myotonic Dystrophy

Mode of transmission, clinical features, name of gene

Answer 3

Autosomal DOMINANT
Gain of function at the mRNA level (3’ untranslated region)
-Triplet repeat expansion disorder, anticipation, and pleiotropy

Question 4

Marfan Syndrome

Mode of transmission, clinical features, name of gene

Answer 4

Autosomal DOMINANT
FBN1
-Has both haploinsufficiency forms and dominate negative forms

Question 5

Osteogenesis imperfecta

Mode of transmission, clinical features, name of gene

Answer 5

Autosomal DOMINANT
COL1A1 and COL1A2
-Brittle bone disease
-Has haploinsuffiency forms, and also dominant negative forms

Question 6

Achondroplasia

Mode of transmission, clinical features, name of gene

Answer 6

Autosomal DOMINANT
FGFR3
-Example of gain of function, unregulated tyrosine kinase signaling
-Nearly 100% penetrance

Question 7

Neurofibromatosis type I

Mode of transmission, clinical features, name of gene

Answer 7

Autosomal DOMINANT
NF1

-Example of AD because of loss of heterozygosity, NF1 as a tumor supressor gene
-highly penetrant but has variable expressivity. High allelic heterogeneity

Question 8

Acute intermittent porphyria

Mode of transmission, clinical features, name of gene

Answer 8

AUTOSOMAL DOMINANT
-Heme synthesis deficiency
-Rare example of an enzyme deficiency that is autosomal dominant (most are recessive)
-AIP is dominant because of high cellular demand for heme
Type of haploinsufficiency

Question 9

Cystic Fibrosis

Mode of transmission, clinical features, name of gene

Answer 9

Autosomal RECESSIVE
-CFTR gene, chloride channel
-highly penetrant

Question 10

Sickle Cell Anemia

Mode of transmission, clinical features, name of gene

Answer 10

Autosomal RECESSIVE
-structural variant of the beta-globin protein in hemoglobin
-Glu6Val

Question 11

Phenylketornuria

Mode of transmission, clinical features, name of gene

Answer 11

Autosomal RECESSIVE
-inability to degrade phenylalanine
-causes brain damage
-PAH gene

Tx: with diet lacking phenylalanine

Question 12

Tay-Sachs Disease

Mode of transmission, clinical features, name of gene

Answer 12

Autosomal RECESSIVE
-Hexosaminidase A deficiency HEXA gene
-Lysosomal storage disease

Question 13

Hemochromatosis

Mode of transmission, clinical features, name of gene

Answer 13

Autosomal RECESSIVE
-Delayed age of onset, and incomplete penetrance
-tendency to accumulate toxic amts of iron

Question 14

Homocystinuria

Mode of transmission, clinical features, name of gene

Answer 14

Autosomal RECESSIVE
Build up of homocysteine

Question 15

Galactosemia

Mode of transmission, clinical features, name of gene

Answer 15

Autosomal RECESSIVE
-Inability to degrade glacatose which is found in the breakdown of lactose

Question 16

Alpha 1-antitrypsin deficiency

Mode of transmission, clinical features, name of gene

Answer 16

Autosomal RECESSIVE
-Leads to adult onset loss of lung elasticity and can cause liver damage in children

Question 17

Severe combined immune deficiency (SCID)

Mode of transmission, clinical features, name of gene

Answer 17

Autosomal RECESSIVE OR X-Linked recessive
-**ADA **gene/Defect in the gamma chain for IL2RG (interleukin)
-d/t build up of adenosine

Good example of Locus Heterogeneity

Question 18

Duchenne Muscular Dystrophy

Mode of transmission, clinical features, name of gene

Answer 18

X-Linked recessive
Sx: Enlarged calves, wasting of thigh muscles
Extremely low genetic fitness (most people with this disease will not be able to mate)-lethal

Question 19

Becker Muscular Dystrophy

Mode of transmission, clinical features, name of gene

Answer 19

X-Linked recessive
Less severe mutation to DMD-will see some genetic fitness

Question 20

Hemophilia A

Mode of transmission, clinical features, name of gene

Answer 20

X-Linked recessive
Deficiency of clotting factor VIII (involves inversions of an intron sequence-incorrect splicing)
Many types of mutations can result in Hemophilia A (allelic heterogeneity

Question 21

What is an obligate carrier?

Answer 21

Obligate=must be a carrier

Question 22

What is skewed X-inactivation?

In regards to Duchenne Muscular Dystrophy

Answer 22

Number of cells contain the active X chromosome with the mutation in DMD are large compared to the functional DMD gene resulting in some symptoms of DMD such as weakness

Question 23

Rett Syndrome

Mode of transmission, clinical features, name of gene

Answer 23

X-dominant
1. Lethal in males
2. Appear normal (6 months) then lose brain function

Question 24

Incontinentia Pigmenti

Mode of transmission, clinical features, name of gene

Answer 24

X-linked dominant
Sx: Manifests as rashes & blisters in early life, learning disability and retinal detachment
Variable expressivity in females (X-inactivation)

Lethal in males

Question 25

Vitamin D resistant Rickets

Answer 25

X-linked dominant

Question 26

Incomplete penetrance definition (reduced)

Answer 26

Not everybody with the mutation displays the phenotype

Question 27

What does Variable Expression mean?

Answer 27

ALL EFFECTED
Some individuals are more effected than others
1. Random chance
2. Other genetic factors (gender)
3. Environmental exposure

Examples: Xeroderma pigmentosum (autosomal recessive), Premenapausal females in Homochromatosis

Question 28

Definition of Pleiotropy

Answer 28

A disease causing mutation that affects more than 1 organ system
Examples: Marfan Syndrome, Osteogenesis imperfecta, CF

Question 29

Locus Heterogeneity definition and example
VS
Allelic Heterogeneity

Answer 29

LOCUS: Mutations of different genes that cause the same disease phenotype

BRCA1/BRCA2=Breast cancer

ALLELIC: Different mutations on the SAME gene cause the disease

Neurofibromatosis