Genetic Disorders - Single gene disorders with nonclassic inheritance

Question 1

3 types of single gene disorders with nonclassic inheritance?

Answer 1

Trinucleotide repeats
Mutations in mitochondrial genes
Genomic imprinting

Question 2

3 types of single gene disorders with nonclassic inheritance?

Answer 2

Trinucleotide repeats
Mutations in mitochondrial genes
Genomic imprinting

Question 3

What nucleotides are usually amplified with trinucleotide repeats?

Answer 3

C and G

Question 4

2 examples of trinucleotide repeat diseases?

Answer 4

Fragile X syndrome

Huntington Disease

Question 5

Trinucleotide repeats often cause _____ diseases

Answer 5

Neurodegenerative diseases

Question 6

Morphologic finding with trinucleotide repeat diseases?

Answer 6

Accumulation of aggregated mutant proteins in large intranuclear inclusions

Question 7

Accumulation of aggregated mutant proteins in large intranuclear inclusions signifies?

Answer 7

Trinucleotide repeat diseases

Question 8

Proclivity to expand with trinucleotide repeat diseases depends strongly on the sex of?

Answer 8

Transmitting parent

Question 9

How is Fragile X syndrome inhertied?

Answer 9

X linked recessive

Question 10

What nucleotides are amplified in Fragile X syndrome?

Answer 10

CGG

Question 11

In what gene and sequence is the trinucleotide mutation for Fragile X syndrome?

Answer 11

FMR1 gene in non-coding sequence

Question 12

The mutation for Fragile X syndrome is classified as?

Answer 12

Loss of function

Question 13

Fragile X syndrome is more common in?

Answer 13

Males

Question 14

Symptoms of Fragile X syndrome?

Answer 14

Long face with large mandible and large ears
Large testicles (macro-orchidism)
Hyperextensible joints
Mitral Valve prolapse

Question 15

Long face with large mandible and large ears and large testicles?

Answer 15

Fragile X syndrome

Question 16

Anticipation

Answer 16

Clinical features worsen with each generation

Question 17

Does Fragile X and Huntington show anticipation?

Answer 17

Yes

Question 18

Carrier _____ are responsible for amplification of CGG repeats for Fragile X

Answer 18

Females

Question 19

Can there be carrier males for Fragile X?

Answer 19

Yes

Question 20

Can carrier females be affected for Fragile X?

Answer 20

Yes

Question 21

2 Fragile X syndromes that have gain of function mutations?

Answer 21

Fragile X associated primary ovarian failure

Fragile X associated tremor/ataxia

Question 22

Who gets Fragile X associated primary ovarian failure?

Answer 22

20% of carrier females

Question 23

Symptoms of Fragile X associated primary ovarian failure?

Answer 23

Menstrual irregularities, decreased fertility and early onset menopause

Question 24

Who gets Fragile X associated tremor/ataxia?

Answer 24

50% of carrier males at age 60

Question 25

Symptoms of Fragile X associated tremor/ataxia?

Answer 25

Intention tremors, cerebellar ataxia, parkinson’s

Question 26

How is Huntington disease inherited?

Answer 26

Autosomal Dominant

Question 27

What gene is mutated and what nucleotide repeat is seen with Huntington disease?

Answer 27

HTT gene

- CAG repeats

Question 28

The mutation for Huntington is classified as?

Answer 28

Gain of function

Question 29

Symptoms of Huntington?

Answer 29

Jerky movements, dementia, dystonic movements

Question 30

Jerky movements, dementia, dystonic movements

Answer 30

Huntington disease

Question 31

mtDNA is entirely from?

Answer 31

Mother

Question 32

mtDNA encodes?

Answer 32

Enzymes in ox. phos.

Question 33

Heteroplasmy

Answer 33

Tissues have BOTH wild type and mutant DNA

Question 34

Tissues have BOTH wild type and mutant DNA

Answer 34

Heteroplasmy

Question 35

Threshold effect

Answer 35

Minimum number of mutant mtDNA that must be present before ox. phos. gives rise to disease

Question 36

Minimum number of mutant mtDNA that must be present before ox. phos. gives rise to disease?

Answer 36

Threshold effect

Question 37

What is an example of a mitochondrial gene mutation disease?

Answer 37

LHON - leber hereditary optic neuropathy

Question 38

Symptoms of LHON (leber hereditary optic neuropathy)?

Answer 38

Bilateral loss of central vision between ages 15-35 that leads to blindness

Question 39

Bilateral loss of central vision between ages 15-35 that leads to blindness

Answer 39

LHON - mitochondrial mutation

- Leber Hereditary optic neuropathy

Question 40

Besides vision loss, what other symptom can be seen with LHON

Answer 40

Cardiac conduction defects

Question 41

When does imprinting occur?

Answer 41

BEFORE fertilization in either the ovum or sperm

Question 42

Maternal imprinting

Answer 42

Silencing of maternal allele

Question 43

Uniparental Disomy

Answer 43

Inherit BOTH chromosomes from 1 parent

Question 44

Defective imprinting

Answer 44

No functional alleles

• paternal carries maternal imprint
• maternal carries paternal imprint

Question 45

Prader Willi syndrome has a deletion of?

Answer 45

15q12 on paternal chromosome

Question 46

Symptoms of Prader willi syndrome?

Answer 46

Short, hyperphagia, obesity, small hands and feet, low IQ

Question 47

Short, hyperphagia, obesity, small hands and feet with low IQ

Answer 47

Prader - willi syndrome

- deletion of 15q12 on paternal chromosome

Question 48

Angelman Syndrome has a deletion of?

Answer 48

15q12 on maternal chromosome

Question 49

Symptoms of Angelman Syndrome?

Answer 49

Inappropriate laughter, seizures, ataxic gait, low IQ

Question 50

Inappropriate laughter, seizures, ataxic gait, low IQ

Answer 50

Angelman Syndrome