HRR: non mendelian genetics I

Question 1

Define non-mendelian genetics

Answer 1

They do not follow classic inheritance patters. This includes trinucleotide repeat disorders, imprinting, mitochondrial disorders, and X-linked inactivation

Question 2

What are trinucleotide repeat disorders

Answer 2

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.

Question 3

What is anticipation?

Answer 3

The number of repeats can further expand from generation to generation. This can cause a more severe or earlier presenting phenotype

Question 4

Which two testing types are often used to diagnosed non-Mendelian genetic disorders?

Answer 4

PCR and southern blot

Question 5

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

Answer 5

fragile X

Question 6

What is the inheritance pattern of Fragile X syndrome

Answer 6

X-linked dominant

Question 7

Name and describe the trinucleotide repeat associated with fragile X syndrome and give the numbers associated with mutation

Answer 7

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

Question 8

How does expansion of fragile X occur

Answer 8

female meiosis

Question 9

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

Answer 9

huntington’s

Question 10

What is the inheritance pattern of huntingtins?

Answer 10

Autosomal dominant with anticipation

Question 11

Describe the trinucleotide repeat associated with huntingtons disease

Answer 11

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

Question 12

how does Huntington’s disease expand?

Answer 12

male meiosis

Question 13

What is the inheritance pattern of myotonic dystrophy?

Answer 13

autosomal dominant with anticipation

Question 14

What trinucleotide repeat is associated with myotonic dystrophy

Answer 14

CTG; normal number of repeats is 5-34, mutation is above 50. 100-1000 is classic, and 1000+ is congenital

Question 15

define myotonic dystrophy

Answer 15

Progressive multisystemic disorder affecting: the skeletal and
smooth muscles, eyes, heart, endocrine system, and central
nervous system

Question 16

Describe the 3 types of myotonic dystrophy

Answer 16

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

Question 17

In congenital myotonic dystrophy, who does the baby get the disorder from

Answer 17

mom

Question 18

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?

Answer 18

Friederich’s ataxia

Question 19

Describe the inheritance pattern of Friederichs ataxia

Answer 19

Autosomal recessive; no anticipation

Question 20

what is the trinucleotide associated with fredriechs ataxia

Answer 20

GAA in intron 1 of FXN

Question 21

What is meant by a primary mitochondrial disorder?

Answer 21

The ETC specifically is not working

Question 22

what is heteroplasmy

Answer 22

in one cell, there can be a mixture of normal and abnormal mitochondria, and the distribution is unpredictable and changes throughout the body

Question 23

What is the threshold effect

Answer 23

The load of specific mitochondrial DNA mutation that any given tissue can tolerate before it shows symptoms

Question 24

describe leigh’s syndrome

Answer 24

a mitochondrial disorder that causes neurologic symptoms, classic MRI changes, and proven mitochondrial dysfunction

Question 25

describe MELAS

Answer 25

a mitochondrial disorder that causes a deficiency in NO. this causes diabetes, stroke-like episodes, neurologic symptoms, hearing issues, GI issues, cardiomyopathy

Question 26

what are CPEO spectrum disorders?

Answer 26

mitochondrial disorders involving a deletion in mitochondrial DNA

Question 27

what is CPEO

Answer 27

a mitochondrial DNA deletion disorder that causes an inability to abduct the eye

Question 28

what is kearn-sayre

Answer 28

a mitochondrial DNA deletion disorder that causes inability to abduct the eye, cardiac issues, neurologic issues, and hearing loss

Question 29

what is pearson’s

Answer 29

a mitochondrial DNA deletion disorder that requires severe transfusion dependent anemia and pancreatic insufficiency

Question 30

which condition can cause enlarged gonads?

Answer 30

fragile X

Question 31

which condition may present with issues with tasks like opening jars, or other tasks involving relaxing a muscle after flexing?

Answer 31

myotonic dystrophy