Genetic Disorders - Single gene disorders with nonclassic inheritance Flashcards
3 types of single gene disorders with nonclassic inheritance?
Trinucleotide repeats
Mutations in mitochondrial genes
Genomic imprinting
3 types of single gene disorders with nonclassic inheritance?
Trinucleotide repeats
Mutations in mitochondrial genes
Genomic imprinting
What nucleotides are usually amplified with trinucleotide repeats?
C and G
2 examples of trinucleotide repeat diseases?
Fragile X syndrome
Huntington Disease
Trinucleotide repeats often cause _____ diseases
Neurodegenerative diseases
Morphologic finding with trinucleotide repeat diseases?
Accumulation of aggregated mutant proteins in large intranuclear inclusions
Accumulation of aggregated mutant proteins in large intranuclear inclusions signifies?
Trinucleotide repeat diseases
Proclivity to expand with trinucleotide repeat diseases depends strongly on the sex of?
Transmitting parent
How is Fragile X syndrome inhertied?
X linked recessive
What nucleotides are amplified in Fragile X syndrome?
CGG
In what gene and sequence is the trinucleotide mutation for Fragile X syndrome?
FMR1 gene in non-coding sequence
The mutation for Fragile X syndrome is classified as?
Loss of function
Fragile X syndrome is more common in?
Males
Symptoms of Fragile X syndrome?
Long face with large mandible and large ears
Large testicles (macro-orchidism)
Hyperextensible joints
Mitral Valve prolapse
Long face with large mandible and large ears and large testicles?
Fragile X syndrome
Anticipation
Clinical features worsen with each generation
Does Fragile X and Huntington show anticipation?
Yes
Carrier _____ are responsible for amplification of CGG repeats for Fragile X
Females
Can there be carrier males for Fragile X?
Yes
Can carrier females be affected for Fragile X?
Yes
2 Fragile X syndromes that have gain of function mutations?
Fragile X associated primary ovarian failure
Fragile X associated tremor/ataxia
Who gets Fragile X associated primary ovarian failure?
20% of carrier females
Symptoms of Fragile X associated primary ovarian failure?
Menstrual irregularities, decreased fertility and early onset menopause
Who gets Fragile X associated tremor/ataxia?
50% of carrier males at age 60
Symptoms of Fragile X associated tremor/ataxia?
Intention tremors, cerebellar ataxia, parkinson’s
How is Huntington disease inherited?
Autosomal Dominant
What gene is mutated and what nucleotide repeat is seen with Huntington disease?
HTT gene
- CAG repeats
The mutation for Huntington is classified as?
Gain of function
Symptoms of Huntington?
Jerky movements, dementia, dystonic movements
Jerky movements, dementia, dystonic movements
Huntington disease
mtDNA is entirely from?
Mother
mtDNA encodes?
Enzymes in ox. phos.
Heteroplasmy
Tissues have BOTH wild type and mutant DNA
Tissues have BOTH wild type and mutant DNA
Heteroplasmy
Threshold effect
Minimum number of mutant mtDNA that must be present before ox. phos. gives rise to disease
Minimum number of mutant mtDNA that must be present before ox. phos. gives rise to disease?
Threshold effect
What is an example of a mitochondrial gene mutation disease?
LHON - leber hereditary optic neuropathy
Symptoms of LHON (leber hereditary optic neuropathy)?
Bilateral loss of central vision between ages 15-35 that leads to blindness
Bilateral loss of central vision between ages 15-35 that leads to blindness
LHON - mitochondrial mutation
- Leber Hereditary optic neuropathy
Besides vision loss, what other symptom can be seen with LHON
Cardiac conduction defects
When does imprinting occur?
BEFORE fertilization in either the ovum or sperm
Maternal imprinting
Silencing of maternal allele
Uniparental Disomy
Inherit BOTH chromosomes from 1 parent
Defective imprinting
No functional alleles
- paternal carries maternal imprint
- maternal carries paternal imprint
Prader Willi syndrome has a deletion of?
15q12 on paternal chromosome
Symptoms of Prader willi syndrome?
Short, hyperphagia, obesity, small hands and feet, low IQ
Short, hyperphagia, obesity, small hands and feet with low IQ
Prader - willi syndrome
- deletion of 15q12 on paternal chromosome
Angelman Syndrome has a deletion of?
15q12 on maternal chromosome
Symptoms of Angelman Syndrome?
Inappropriate laughter, seizures, ataxic gait, low IQ
Inappropriate laughter, seizures, ataxic gait, low IQ
Angelman Syndrome
