Genetics

Question 1

Gene that encodes ATP-gated chloride channel that secretes Cl- in the lung, GI tract and sweat glands
mutation is misfolded protein that is retained in the RER
AR

Answer 1

CFTR
Phe508 deletion
Cl- > 60 mEq/L in sweat is diagnostic
Newborn: meconium ileus
deficiency: ADEK vitamins (pancreatic insuff)

Question 2

truncated dystrophin protein
X-linked frameshift mutation
accelerated muscle breakdown with pelvic girdle weakness and superior progression
Pseudohypertrophy of calf muscle from fibrofatty replacement
Gower maneuver to aid standing
Cause of death: dilated cardiomyopathy

Answer 2

Duchenne muscular dystrophy
Gene: DMD
dystrophin connects actin to ECM
Lab: Increased CPK & aldolase
Dx: bx and Western blot

Question 3

point mutation in dystrophin

onset in adolescence or early adulthood

Answer 3

Becker muscular dystrophy

Question 4

muscle wasting, frontal balding, cataracts, testicular atrophy, arrhythmia
CTG repeat expansion of DMPK gene

Answer 4

myotonic dystrophy (type 1)

Question 5

CGG trinucleotide repeat
altered expression of FMR1 gene due to methylation
X-linked defect
Genetic mental retardation
Post-pubertal enlarged testes, long face with large jaw, large everted ears, autism, mitral valve prolapse

Answer 5

Fragile X syndrome

Question 6

Brushfield spots
ASD
intellectual disability, flat facies, prominent epicanthal fold, single palmar crease, gap between 1st and 2nd toes, duodenal atresia, increased risk of ALL, AML and Alzheimer disease
meiotic nondisjunction -> advanced maternal age

Answer 6

Trisomy 21

Question 7

severe intellectual disability
rocker bottom feet
micrognathia
low-set ears, prominent occiput
clenched hands
congenital heart disease
death within 1 year

Answer 7

Trisomy 18 = Edwards syndrome
Lab: decreased PAPP-A, free beta-hCG in trimester
Quad screen: decreased AFP, beta-hCG, estriol, decreased normal inhibin A

Question 8

severe intellectual disability
rocker bottom feet
microphthalmia
microcephaly
cleft lip/palate
holoprosencephaly
polydactyly
congenital heart disease

Answer 8

Patau syndrome = trisomy 13
1st trimester screen: decreased free beta-hCG, PAPP-A,
increased nuchal translucency

Question 9

occurs when long arms of 2 acrocentric chromosomes fuse at the centromere with loss of the 2 short arms

Answer 9

Robertsonian translocation
balanced = no problem
unbalance = miscarriage, stillbirth, chromosome imbalance

Question 10

congenital microdeletion of short arm of chromosome 5
microcephaly
moderate to severe intellectual disability
high-pitched cry
epicanthal folds
VSD

Answer 10

Cri-du-chat syndrome

Question 11

congenital deletion of long arm of chromosome 7 (includes elastin gene)
elfin facies, intellectual disability,
hypercalcemia** (increased sensitivity to Vit D)
extreme friendliness to strangers
cardiovascular problems

Answer 11

Williams syndrome

Question 12

22q11 deletion syndromes

Answer 12

DiGeorge syndrome

Velocardiofacial syndrome

Question 13

one gene contributes to multiple phenotypic effects

Answer 13

pleiotropy

Question 14

tumor suppressor gene mutation that is expressed when complementary allele is deleted/mutated

Answer 14

loss of heterozygosity

This does not happen with oncogenes

Question 15

nonfunctional altered protein prevents normal gene product from functioning

Answer 15

dominant negative mutation

Question 16

both alleles contribute to the phenotype of the heterozygote

Answer 16

codominance

ex: blood groups; alpha1-antitrypsin deficiency

Question 17

not all individual with a mutant genotype show the mutant phenotype

Answer 17

incomplete penetrance

Question 18

mutations at different loci can produce a similar phenotype

Answer 18

locus heterogeneity

ex: albinism

Question 19

different mutations at the same locus can produce a similar phenotype

Answer 19

allelic heterogeneity

ex: beta-thalassemia

Question 20

presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrial inherited disease

Answer 20

heteroplasmy

Question 21

methylation of one allele makes it inactive

deletion of the active allele produces disease

Answer 21

imprinting

Question 22

gene from dad is silent (imprinting); maternal gene deleted/mutated
inappropriate laughter, seizures, ataxia, severe intellectual disability
“happy puppet”

Answer 22

Angelman syndrome
Paternal imprinting
“Angel’s daddy is silent in church but laughs at inappropriate jokes”

Question 23

gene from mom is silent; paternal gene is mutated/deleted
hyperphagia, obesity, intellectual disability,
hypogonadism, hypotonia

Answer 23

Prader-Willi
Maternal imprinting
“willi’s mama is silent when she’s overeating”

Question 24

mnemonic for blotting procedures

Answer 24

SNoW DRP
Southern blot = DNA
Northern blot = RNA
Western blot = protein ex: HIV

Question 25

blotting technique to identify DNA-binding proteins

Answer 25

Southwestern blot

Question 26

often present with myopathy, lactic acidosis, & CNS disease
secondary to failure in oxidative phosphorylation
muscle bx: ragged red fibers

Answer 26

mitochondrial myopathies

Question 27

AD

mutation in PKD1

Answer 27

polycystic kidney disease

Question 28

AD

mutations of APC gene on chromosome 5

Answer 28

FAP

familial adenomatous polyposis

Question 29

AD

mutation in fibrillin-1 gene

Answer 29

Marfan

CT disorder, pectus excavatum, aortic incompetence -> aneurysms, floppy mitral valve, subluxation of lenses

Question 30

AD

mutation in NF1 gene on chromosome 17

Answer 30

neurofibromatosis type 1

Question 31

AD
bilateral acoustic schwannomas, juvenile cataracts
mutation on chromosome 22 NF2

Answer 31

neurofibromatosis type 2

Question 32

AD
numerous benign hamartomas
incomplete penetrance & variable expression

Answer 32

tuberous sclerosis

Question 33

deletion of VHL gene on chromosome 3

development of multiple tumors

Answer 33

von Hippel-Lindau disease

Question 34

AD
mutations of RET
familial tumors of endocrine glands

Answer 34

MEN2A & 2B