HRR: non mendelian genetics I Flashcards
Define non-mendelian genetics
They do not follow classic inheritance patters. This includes trinucleotide repeat disorders, imprinting, mitochondrial disorders, and X-linked inactivation
What are trinucleotide repeat disorders
When a normal sequence of 3 repeated nucleotides becomes too expanded (aka there’s too much repeating), disruption of protein function or gene expression can occur.
What is anticipation?
The number of repeats can further expand from generation to generation. This can cause a more severe or earlier presenting phenotype
Which two testing types are often used to diagnosed non-Mendelian genetic disorders?
PCR and southern blot
Rodger is a 5 year old male with a history of developmental delays, autism and significant behavior issues. Features on exam are consistent with long face and both prominent forehead and ears. He has an uncle and brother with a similar history of developmental delays.
what condition would you screen for
fragile X
What is the inheritance pattern of Fragile X syndrome
X-linked dominant
Name and describe the trinucleotide repeat associated with fragile X syndrome and give the numbers associated with mutation
CGG in promoter region of FMR1 gene; expansion and methylation of this repeat can cause issues. Normal is 5-54, full mutation is greater than 200
How does expansion of fragile X occur
female meiosis
Fred is a 55 yo presenting for
a routine physical exam. Past medical history notable for
depression, bipolar, and recent
cognitive decline. On exam, you notice dancing-like
movements
what condition are you screening for
huntington’s
What is the inheritance pattern of huntingtins?
Autosomal dominant with anticipation
Describe the trinucleotide repeat associated with huntingtons disease
CAG in 1st exon of HTT gene. Normal number of repeats in 26, full mutation is greater than 36. For full mutation, full penetrance is 40-50 and juvenile onset is greater than 60
how does Huntington’s disease expand?
male meiosis
What is the inheritance pattern of myotonic dystrophy?
autosomal dominant with anticipation
What trinucleotide repeat is associated with myotonic dystrophy
CTG; normal number of repeats is 5-34, mutation is above 50. 100-1000 is classic, and 1000+ is congenital
define myotonic dystrophy
Progressive multisystemic disorder affecting: the skeletal and
smooth muscles, eyes, heart, endocrine system, and central
nervous system
Describe the 3 types of myotonic dystrophy
oMild: cataracts and mild myotonia (delayed relaxation after contraction)
oClassic: muscle weakness of hands and face, myotonia, cataracts, cardiac abnormalities, and other systemic issues
oCongenital: hypotonia and severe weakness at birth. Often there is respiratory insufficiency and early death, and associated intellectual deficiency is common
In congenital myotonic dystrophy, who does the baby get the disorder from
mom
Tina is a 16 year old female presenting due to
changes in her speech and gait. She has recently been having trouble pronouncing her
words, walking upstairs and maintaining her balance. Mother has noticed she grabs on to things more often to assist in mobility
what condition are you screening for?
Friederich’s ataxia
Describe the inheritance pattern of Friederichs ataxia
Autosomal recessive; no anticipation
what is the trinucleotide associated with fredriechs ataxia
GAA in intron 1 of FXN
What is meant by a primary mitochondrial disorder?
The ETC specifically is not working
what is heteroplasmy
in one cell, there can be a mixture of normal and abnormal mitochondria, and the distribution is unpredictable and changes throughout the body
What is the threshold effect
The load of specific mitochondrial DNA mutation that any given tissue can tolerate before it shows symptoms
describe leigh’s syndrome
a mitochondrial disorder that causes neurologic symptoms, classic MRI changes, and proven mitochondrial dysfunction
describe MELAS
a mitochondrial disorder that causes a deficiency in NO. this causes diabetes, stroke-like episodes, neurologic symptoms, hearing issues, GI issues, cardiomyopathy
what are CPEO spectrum disorders?
mitochondrial disorders involving a deletion in mitochondrial DNA
what is CPEO
a mitochondrial DNA deletion disorder that causes an inability to abduct the eye
what is kearn-sayre
a mitochondrial DNA deletion disorder that causes inability to abduct the eye, cardiac issues, neurologic issues, and hearing loss
what is pearson’s
a mitochondrial DNA deletion disorder that requires severe transfusion dependent anemia and pancreatic insufficiency
which condition can cause enlarged gonads?
fragile X
which condition may present with issues with tasks like opening jars, or other tasks involving relaxing a muscle after flexing?
myotonic dystrophy
