Med_Gen_Con_2-_2021-2022-LEO
pdf
keyboard_arrow_up
School
Bronx High School of Science *
*We aren’t endorsed by this school
Course
1A
Subject
Medicine
Date
Dec 6, 2023
Type
Pages
3
Uploaded by DukeRainSalmon32
1
MEDICAL GENETICS CONFERENCE 2
1.
A 46-year-old female consulted her family physician. She had noted that she had passed some blood in
her stool several times in the previous 3 months, which she attributed to hemorrhoids. Over the past 12
months her appetite had decreased, and she lost over 10 pounds. The patient revealed that her father and
paternal grandfather had died of colon cancer. The physician suspected that the patient might have
colorectal cancer, so he requested that she submit 3 consecutive daily fecal specimens for occult blood
tests. All stool samples returned with positive results. The patient was also diagnosed with microcytic
anemia. A colonoscopy was performed and revealed the presence of a moderately large tumor (~5-6 cm)
in the proximal colon (proximal to the splenic flexure). A biomarker for colorectal cancer,
carcinoembryonic antigen, was elevated (20 μg/L; normal; 0
-
3 μg/L). Surgery was performed, where the
tumor was resected and end-to-end anastomosis was performed. The patient was diagnosed with
Lynch
Syndrome which is also known as hereditary nonpolyposis colorectal cancer (HNPCC).
A.
What pathway is mutated in this female? Describe how this mutation(s) leads to cancer.
B.
What is the mechanism of inheritance? What is the probability that her children will inherit
HNPCC?
C.
What environmental factors contribute to the pathology of colorectal cancer? People with
HNPCC have a higher risk of developing other cancers – what are they?
Information:
Lynch Syndrome is the most common form of hereditary colon cancer, accounting for about 2
-7%
of all colorectal cancer diagnoses each year. People with Lynch often have at least 3 family members and 2
generations with colorectal cancer and/or endometrial
cancer, and cancer develops before age 50 (compared to 60
for sporadic colon cancer). Although not everyone who carries a Lynch Syndrome pathogenic variant will develop
colorectal cancer, the risk is very high.
https://www.slideserve.com/china/mlh1
-hereditary-non-polyposis-colon-cancer-hnpcc
2.
Ryan, a 15-year-old boy, was referred to a neurologist due to generalized muscle weakness, myoclonus
and ataxia. Further examinations revealed sensorineural hearing loss, slowed nerve conduction velocities, and
mildly elevated blood and cerebrospinal fluid lactate levels.
His family history revealed a maternal uncle who
died of an undiagnosed myopathic disorder at 53 y
ears; a maternal aunt with progressive dementia who
presented with ataxia at 37 years; and an 80
-year-old maternal grandmother with deafness, diabetes and renal
dysfunction. Molecular testing of a skeletal muscle biopsy identified abnormal mitochondria, with a
heteroplasmic mutation (8344G>A), a mutation known to be associated with myoclonic epilepsy with ragged
-
red fibers (MERRF).
A.
What is the mechanism of inheritance of MERRF? What would be the risk that this patient
could pass this mutation to his offspring?
B.
How does this mutation result in abnormal mitochondria?
C.
What accounts for the increased lactate in this child’s blood and cerebrospinal fluid? Why do
you think this child was not phenotypically affected until he reached the age of 15?
D.
What is heteroplasmy?
2
3.
In the second year of your Pediatric residency, you encounter Jake, a 9-year-old male, at the Pediatric
clinic. Jake was born at full-
term weighing 7 pounds, 8 ounces and appeared normal. However, as he grew older
his mother noted that he missed several developmental milestones and appeared to have several dysmorphic
features such as a long face, high forehead, large jaw with prominent chin and large, poorly formed ears.
In
addition, you noticed that Jake was hyperactive and displayed poor eye contact, frequent hand flapping and
unusual responses to various touch, auditory and visual stimuli. Chromosomal analysis revealed the presence of
a “constriction site” on Jake’s X chromosome. Further genetic analysis identified the pre
sence of a GCC
trinucleotide repeat within the promoter region of the Fragile X Mental Retardation 1 (FMR1) gene on the X
chromosome. This mutation leads to the silencing of the FMR1 gene and a lack of its product.
DNA analysis of
both of Jake’s sisters r
evealed the presence of this GCC repeat; one sister was found to have an IQ of 65;
whereas the other sister’s IQ was within normal range.
A.
How does expansion of CpG in the promoter region result in suppression of FMRP
expression?
What mechanism is faulty that may allow this expansion to occur?
B.
Fragile X syndrome appears to be inherited in a dominant manner but not all females have
Fragile X Syndrome or if they do, their symptoms are not as severe. Why?
C.
What is a premutation?
What is anticipation?
D.
Recent studies are investigating 5-aza-2-deoxycytidine as a treatment for Fragile X
Syndrome. What is the rationale for investigating this compound?
Information
: Fragile X mental retardation (FMR) is characterized by moderate to severe intellectual delay,
macroorchidism (abnormally large testes), and distinct facial features, including long face, large ears, and
prominent jaw. It is considered to be X-linked
disease with variable penetrance, affecting 1 in 4000 males and
1 in
8
000 females. Accounts for 3-5% of inherited intellectual disability among boys
(Genetic Home Page; US
National Library of Medicine)
.
This methylation of FMR1 in chromosome band Xq27.3 is believed to
result in constriction of the X chromosome which was called a 'fragile'
site in the pastwhen karyotype was the standard diagnostic test
performed , a phenomenon that gave the syndrome its name.
FMR protein is found throughout the body, but in highest
concentrations within the brain and testes. It appears to be primarily
responsible for selectively binding to around 4% of mRNA in
mammalian brains and transporting it out of the cell nucleus and to the synapses of neurons.
3
4.
A young couple wanting to start a family was referred to genetic counseling as the wife has a brother
who has cystic fibrosis. The wife does not have the disease, but she and her brother tested positive for the
ΔF508
mutation. The husband was then tested for the
ΔF508 mutation and was found to be negative. They have a baby
girl, Ariel, whose newborn screening results were normal. However, at 1 year of age Ariel was admitted to
Westchester Medical Center suffering from a chronic cough and was having frequent diarrhea. The parents were
also worried because Ariel’s weight and height plotted less than the third percentile. Upon arriving at the
emergency room, the attending pediatrician noted that salt crystals were present on Ariel's skin and called Dr.
Clarick, a pediatric pulmonologist. The pulmonologist ordered a test for sweat chloride concentration by
pilocarpine iontophoresis; the sweat chloride level was 75 mmol/L leading Dr. Clarick to suspect that Ariel may
be suffering from cystic fibrosis.
A. What is the mechanism of inheritance of cystic fibrosis? What protein is defective?
B.
What accounts for the fact that this child has cystic fibrosis, but the father tested negative for ΔF508
mutation?
C.
Considering what you know about protein synthesis and trafficking, discuss the many different types
of mutations that result in Cystic Fibrosis.
D.
Recent advances lead to the approval of Lumacaftor, ivacaftor, or combinatio
n of
elexacaftor/ivacaftor/tezacaftor (Trikafta) for Cystic Fibrosis. Do you think the drug should be given
to Ariel?
Your preview ends here
Eager to read complete document? Join bartleby learn and gain access to the full version
- Access to all documents
- Unlimited textbook solutions
- 24/7 expert homework help