Genetic Diseases III Flashcards
Is Huntington’s passed on in an AD or AR way?
AD
What is inheritance pattern of Fragile X syndrome? Penetrance?
XLD with reduced penetrance
What is the protein that is affected in fragile x syndrome? What is the trinucleotide repeat?
FMR-1 protein
CGG
What is the protein that is affected in Huntington’s disease? What is the trinucleotide repeat?
Huntingtin
CAG
How many triplet repeats can one have with Huntington’s diseases before symptoms set it?
35
Where is the triplet repeat found in Huntingtons (intron extron, UTR)?
Exon
Where is the triplet repeat found in fragile X (intron extron, UTR)?
UTR
What is anticipation?
Diseases that get worse or expressed earlier in successive generations
What is the phenomenon of a slowly expanding trinucleotide repeat number from a normal size to a disease-causing mutation?
Amplification
True or false: triplet repeats always or almost always increase in successive generations
False–mostly stay the same
Genes with repeat sizes that are larger than normal, but still small enough to not cause clinical problems are called what?
Intermediate alleles
What is the leading cause in INHERITED mental impairment and the leading known signlepgene cause of ASD?
Fragile X syndrome
What fraction of children diagnosed with fragile X sydrome have autism?
1/3
Who are affected worse in fragile X syndrome, males or females?
Males
What is the affected range of fragile X syndrome?
> 200
True or false: an allele in the premutation range (for fragile X syndrome) always changes is size
True
True or false: expansion from pre to full mutation of fragile x sydrome only occurs through males
False–only through females
What are the physical signs of fragile x syndrome? (3)
Protruding jaw, elongated ears, big testicles
What chromosome is the huntingtin gene on?
4
People who have between 26-36 CAG repeats have what predisposition?
No disease, but the repeats are likely to expand in offspring
What are the symptoms of huntington’s?
Jerky movements (chorea)
Depression/irritability
Behavior problems
What is the region of the brain that is affected in Huntingtons?
Caudate nucleus
Greater than what number of CAG repeats causes juvenile onset of huntingtons?
60
What is a balanced translocation?
Where equal parts of a chromosome are exchanged
What is Robertsonian translocation?
q and p parts of a chromosome are translocated, resulting in a really small chromosome, and a large chromosome. Often the small one is lost
What are chromosomal pericentric and paracentric inversions?
Where part of a chromosome is flipped within itself (pericentric)
When two parts of a chromosome are invertedaround the centromere
What are isochromes?
Splitting of a chromosome in the wrong direction at the centromere
Trisomy 18 = ?
Edward’s syndrome
What are the signs of Edward’s syndrome?
MR
Prominent occiput
Micrognathia
What are the heart defects in Edward’s syndrome?
ASDs
What is the classic renal malfomation in Edward’s sydrome?
Horseshoe kidney
What is the foot characteristic of Edward syndrome?
Rocker bottom feet
What is the finger characteristics of edwards syndrome?
Syndactyly
What is the hip characteristics of Edward’s syndrome?
Abducted hips
What are the head defects of Edward’s syndrome?
MR
Prominent occiput
Micrognathia
What is the finger characteristics of edwards syndrome?
Syndactyly
Trisomy 13 = ?
Patau sydrome
What is the finger characteristics of Patau syndrome?
Polydactyly
What is the abdominal characteristics of Patau syndrome?
Umbilical hernia
What are the head characteristics of Patau syndrome? (4)
Cleft lip/palate
Microphthalmia
Microcephaly
MR
45X = ?
Turner’s syndrome
47 XXY = ?
Klinefelter’s syndrome
What is the sex in Turner’s syndrome?
Female
What is the cause of monosomy?
Sperm does not deliver the chromosome it was supposed to
What percent of fetuses with turner’s syndrome are miscarried?
99%
What fraction of pts with Turner’s syndrome have 45X?
1/2 (others are mosaics and others)
What are the physical findings of Turner’s syndrome?
Webbed neck
Puffy hands and feet
Low set ears
What are the heart defects found in Turner’s syndrome?
Bicuspid valve disorders
Correction of the aorta
What forms the webbed neck found in Turner’s syndrome?
Cystic hygroma (Failure of lymphatics to form and drain properly)
What are the chest characteristics of Turner’s syndrome?
Broad based nipples
Broad chest
What are the hand characteristics of Turner’s syndrome?
Short 4th metacarpal
What are the skin findings of Turner’s syndrome?
Pigmented nevi
What are the ovarian findings of Turner’s syndrome?
Streaked ovary
When in life are Turner’s syndrome pts found to have the disease?
Puberty d/t failure to grow
What is the most common cause of primary amenorrhea?
Turner’s syndrome
What are the physical findings of Klinefelter’s syndrome? (4)
Poor beard growth
Small genitalia
Gynecomastia
Mild IQ loss
What CA are Klinefelter syndrome pts predisposed to? Why?
Breast CA d/t hyperestrogenism
What are the histological findings in testicles of pts with Klinfelter’s syndrome?
Hylaine deposits in the seminal vesicles
Methylated genes are expressed or not?
Not
Acetylated gene are expressed or not?
Are
True or false: genes inherited from mom/dad are inherited with a preset methylation
True
What is the chromosomal change involved in Angelman syndrome?
Maternal chr 15 partial del results in no AS gene
What is the chromosomal change involved in Prader-Willi syndrome?
Paternal chr 15 partial del results in no PWS gene
What is the normal methylation pattern of the AS gene on the maternal chromosome 15? Father?
Father = off Mother = on
What is the normal methylation pattern of the PWS gene on the maternal chromosome 15? Father?
Father = on Mother = off
Paternal deletion of chromosome 15 = ?
PWS
Maternal deletion of chromosome 15 = ?
Angelmann syndrome
Maternal deletion of chromosome 15 = ?
Angelman syndrome
What are the symptoms of PWS? (3)
Overeating
MR
Small genitals and hands
What are the symptoms of Angelman syndrome?
Severe MR
Odd laughing
Spasticity
Ataxia
