Lecture 17 Flashcards
Fragile X syndrome is an X-linked ______ disorder caused by mutation in FMR1 gene. Mental developmental symptoms include non-progressive moderate to severe ______ in males. Similar symptoms can range in females and are often much less severe. Physical appearance of these patients includes long ____, big ____, and hyperextendable joints.
X-linked DOMINANT
Retardation
Face
Ears
How often do males affected with fragile X syndrome have affected daughters when mating with a normal female?
NEVER. Affected Males never have affected daughters.
What is the relationship between the risk of a normal phenotype mother having an affected offspring and the size of the CGG repeat in the 5’ UTR region of her FMR1 gene (Sherman Paradox)?
The larger the CGG repeat is, the greater risk there is for her offspring to exhibit a full expansion and thus become affected.
What is the accepted cutoff of CGG repeats in the 5’ UTR of the FMR1 gene that will NOT lead to expansion and risk of fragile X syndrome in the offspring and what is the number above which the repeat expansion is guaranteed?
Less than 50 CGG repeats is associated with no risk of having a fragile X affected offspring, while 90+ is associated with 100% exhibiting the expansion.
Myotonic Dystrophy is an Autosomal ______ disease.
Autosomal DOMINANT disease
DMPK (Dystonia Myotonum Protein Kinase) - the protein involved with Myotonic Dystrophy (MD) - has a ____ repeat in the _____ UTR of the gene.
It has a CTG repeat in the 3’ UTR of the gene
Unlike with Fragile X syndrome, MD expansions increase from generation to generation, leading to worsening and earlier onset of symptoms. This is called _____.
ANTICIPATION.
The normal limit for CTG repeats in the MD gene is _____ or less.
40 or less
The mRNA produced from the CTG repeat in MD is a toxic _____ of function RNA. It binds up other ______ needed for other ______.
It is a toxic GAIN of function. It binds up other factors needed other transcripts.
Another cause of MD is a CCTG repeat in the first _____ of the DM-2 gene, and it is also considered a _____ of function.
The repeat is in the first INTRON, and it is also considered a GAIN of function.
Huntington’s disease is Autosomal ______.
Autosomal DOMINANT
Huntington’s disease is caused by a ______ repeat in the _____ region of the HD gene. It is considered a ______ of function mutation.
It is caused by a CAG repeat in the CODING region of the HD gene. It is considered a GAIN of function mutation.
How does Anticipation differ with HD when compared to MD?
There is full penetrance in HD, and the anticipation refers only to the age of onset of symptoms, as opposed to age of onset AND severity as seen in MD.
Androgen receptor (X-linked) diseases could be gain of function or loss of function. What is an example of each?
Gain of function in AR receptor = Kennedy Disease
Loss of function in AR receptor = complete testicular feminization (complete gene knockout.)
