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Flashcards in Genetics Diseases Deck (180):
1

reciprocal transformation of hematopoietic stem cells results in

CML: Chronic Myeloid Leukemia

2

Gene that causes hypertrophic cardiomyopathy

MYBPC3 ((cardiac) myosin binding protein C)

3

RTK oncogene involved in Acute Lymphoblastic Leukemia

FLT3

4

drug that inhibits FLT leukemic oncogene

Sutent (Sunitinib)

5

CML phase characterized by <10% blasts

chronic

6

CML phase characterized by 10-20% blasts

accelerated

7

CML phase characterized by >20% blasts

blast crisis (acute)

8

type of hematopoietic cell present in CML

myeloblast

9

Philadelphia chromosome translocation causes

CML

10

Philadelphia chromosomal translocation is which kind of translocation

reciprocal

11

caused by LMNA gene cryptic splice site
misshaped nuclear lamina
short stature, low body weight, early hair loss, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, premature aging.
Note: normal mental progression bc LMNA not expressed in brain

alien-like appearance but normal IQ

Hutchinson-Gilford Progeria

12

Achondroplasia: mendelian or polygenic?

mendelian

13

Pompe: mendelian or polygenic?

mendelian

14

MS (Multiple Sclerosis): mendelian or polygenetic?

polygenic

15

benign, cutaneous, plexiform tumors along nerve
mendelian, autosomal DOMINANT
chrom 17

Neurofibromatosis Type 1

16

3 examples of diseases involving GERMLINE mutation?

Hereditary RB,
Familial Adenomatous Polyposis,
Multiple Endocrine Neoplasia 2B

17

6 examples of autosomal recessive disorders

albinism
CF
PKU
SCA
TS
HI (harlequin ichthyosis)

18

3 examples of autosomal DOMINANT disorders

Marfan
Neurofibromatosis (type 1)
Brachydactyly

19

4 examples of autosomal RECESSIVE CANCERS

Ataxia telangiecatasia (lymphoma)
Bloom (tumors)
Xeroderma pigmentosum (skin cancer)
fanconi's anemia (FA) (AML, acute myeloid leukemia)

20

This kind of inherited disorder confers malaria resistance

Autosomal recessive

21

5 examples of autosomal DOMINANT CANCERS

Familial/hereditary RB
Familial adenomatous polyposis (APC)
Colorectal cancer (hereditary nonpolyposis)
Wilms (WT1)
Breast and ovarian cancer (BRCA1)

22

BRCA1 tumor suppressor loss of function mutation seen in hereditary breast and ovarian cancer follows what inheritance pattern

Autosomal dominant

23

7 examples of X-linked RECESSIVE inheritance

Hemophilia
Color blindness
Duchenne MD
Becker MD (milder)
Lesch-Nyhan
Nephrogenic diabetes insipidus

24

2 examples of X-linked DOMINANT

hypophosphatemic rickets (HR)
Fragile X

25

mutations in ESCO2
sister chromatids lack cohesion d/t premature centromere separation
phocomelia: congenital defect, hands and feet attached to abbreviated arms and legs
high LOD score indicating genetic linkage
what disease?

Roberts

26

defect in ATP binding cassette (ABC) transporter
maternal nonsense mutation
paternal splice variant
autosomal RECESSIVE inheritance
hyperkeratosis
ectropion
eclabium

Harlequin ichthyosis (HI)

27

T/F: majority of retinoblastoma patients have family history of RB

false, most RB patients have no family history of RB.

28

Hereditary RB requires ___ mutation(s) for patient to acquire RB

1 (1 preexisting germline mutation)
(2 hit hyp)

29

Non-hereditary RB requires ___ mutation(s) for patient to acquire RB

2
(2 hit hyp)

30

mitochondrial disease
maternally inherited
mutation in NADH dehydrogenase
degeneration of optic nerve Retinal Ganglion Cells (RGCs)

S/Sx:
loss of central vision
affects males more frequently

Leber's hereditary optic neuropathy (LHON)

31

mitochondrial disease
maternally inherited
mutation in tRNA or rRNA (not mRNA)
varying degrees of expressivity d/t heteroplasmy

S/Sx:
ataxia, epilepsy

no cure, treatment sx

MERRF (Myoclonic Epilepsy ass.w/ Ragged Red Fibers)

32

mitochondrial disease
maternally inherited through egg
mutations in tRNA

S/Sx:
late onset
muscle weakness, neuro defects
lactic acidosis
stroke-like episodes
vision loss
dementia

MELAS (Myopathy, encephaly w/ Lactic Acidosis and Stroke)

33

deletion of mtDNA
paralysis of eye muscles
hearing loss
early onset

KSS
(Kearns-Sayre Syndrome)

34

Although Fragile X follows an X linked dominant inheritance pattern, it appears to follow an X linked recessive pattern in females due to

X inactivation

35

Females experience variable exressivity of Nephrogenic diabetes insipidus due to

X inactivation

36

45, XO
short stature, neck webbing,
bicuspid aortic valve
normal IQ
no barr bodies (only 1 X-->active)

Turner

37

47, XXY
48, XXYY
48, XXXY
49, XXXXY
Extra X(s) MALES
males w/ tall stature, hypogonadism, infertility
learning difficulties
1 barr body (1 active, 1 inactive when XXY)

Klinefelter

Mr. Kline (males)

38

47, XXX
Extra X FEMALES
tall, reduced intelligence
2 barr bodies
(1 active so 2 inactive)

Trisomy X

39

random x inactivation may lead to expression of X linked recessive traits such as _____,_______,______ in females

nephrogenic diabetes insipidus
Duchenne MD
Becker MD

40

rate viability between Trisomy 13,18,21

21>18>12

41

+13

Patau, risk of miscarry, poor prognosis

42

+X FEMALE

Triple X

43

+X MALE

Klinefelter

Mr. Kline

44

47, XY, +18; 47, XX, +18 (most female)

Edwards (Trisomy 18)

45

47, XX, +21; 47, XY, +21
result of ROBERTSONIAN translocation

Down (Trisomy 21)

46

+18
S/Sx:

Low birthweight, irregularly shaped head, ears below eye line, cleft lip, heart, kidney defects

47

diandric refers to

in TRIPLOIDY, 2 paternal sets and 1 maternal set
XYY
MORE COMMON than dygynic
near normal size child
macrocephaly, syndactyly of 3rd/4th fingers

48

digynic refers to

in TRIPLOIDY, 2 maternal sets, 1 paternal set
XXY
much more SEVERE: intrauterine growth retardation,
macrocephaly, syndactyly of 3rd/4th fingers

49

digynic triploidy results in severe intrauterine growth defects such as:

intrauterine growth retardation, macrocephaly, syndactyly of 3rd/4th fingers

50

individual is often unaffected but increased risk of miscarriage and children with anomalies in what kind of translocation

balanced/reciprocal

51

46,XY,t(1;2)(p32;q22)

Balanced translocation carrier in a male between 1p32 and 2q22.

52

46,XX,der(7),t(7;12)(p15.2;q24.11)pat

der(7): indicates a loss of genetic material from chromosome 7, the
translocation affects chromosome bearing the 7 centromere.
pat: paternal (inherited from father with a balanced translocation)

Interpretation: A female with an unbalanced translocation between chromosomes 7 and 12 which results in a deletion (or monosomy) of 7p15.2 to terminus and duplication (or trisomy) of 12q24.11 to terminus. The father is a balanced translocation carrier.

53

translocation between acrocentric (13,14,15, 21,22) chromosomes

Robertsonian

54

this kind of translocation yields metacentric or submetacentric chromosome and loss of short (p) arms on from acrocentric chromosome

Robertsonian

55

45,XX,der(14;21)(q10;q10)

Interpretation: a female who is a balanced carrier for chromosomes 14 &21 Robertsonian translocation

56

46,XX,+21,der(14;21)(q10;q10) mat

Interpretation: a female with trisomy 21 secondary to a maternally inherited 14&21 Robertsonian translocation

57

Trisomy 14, Monosomy 14, and Monosomy 21 are (viable or inviable)

inviable

58

in this type of translocation, carrier is unaffected but risk of infertility or children with unbalanced translocations leading to inviability

Robertsonian

59

most common Robertsonian translocation

13q14q
(note: Robertsonian carriers at risk for children with +13 (patau), trisomy 14(inviable), monosomy 14 (inviable), monosomy 21 (inviable), or +21 (down))

60

inviable zygotes in this type of chromosomal inversion

ParAcentric
(arm, not involving centromere)

61

risk for children with duplication & deletion in this kind of chromosomal inversion

Pericentric

chance of liveborn (not inviable) like ParAcentric

62

46,XX,inv(2)(q15q36) de novo

female with a paracentric inversion (same side of centromere;
-you know it's parAcentric b/c if it involved centromere (pericentric) it would involve both arms
q15q36) of chromosome 2.
De novo: The parents have been karyotyped and neither has the inversion

63

46,XX,inv(6)(p22q15)pat

-you know it's pericentric (in centromere) bc it involves both arms
Interpretation: Male with a pericentric inversion of chromosome 6 (involves
centromere). The breakpoints are at band p22 (short arm) and q15 (long arm)
and the material between these two breaks has been inverted. This inversion
was inherited from his father.

64

46,XY,del(9)(p13.2)

Interpretation: Male with terminal deletion of 9p13.2. All
material distal (with respect to centromere) to band p13.2 is
lost.

65

46,XX,dup(9)(q22.32q33.1)

Interpretation: Female with interstitial duplication of genetic
material between bands 9q22.32 to 9q33.1.

66

marker chromosome
coloboma of Iris, retina, or choroid
heart defects, kidney malformations, anal anomalies, cleft palate, ear tags
intelligence varies

Cat Eye Syndrome due to MARKER chromosome

67

2 p arms, 2 q arms

isochromosome

68

isochromosome tetrasomy (2 p arms, 2 q arms)

S/Sx:
mosaicism, intellectual disability, sparse hair, unusual skin coloring, cleft palate, heart defects, hearing loss, seizures, vision impairment, genital anomalies, diaphragmatic hernia

Pallister-Killian

69

breaks on both p and q arms, ends fuse
deletion of distal material, partial monosomy
"dynamic mosaicism"
developmental delay

ring chromosome (immediately think TURNER...ring turns and turns)

70

ring
45, XO
lymphedema, webbed neck, aortic stenosis, short stature, infertility, widely spaced nipples, learning difficulty
"dynamic mosaicism"

Turner

71

46,XX[2] / 45,X[18]

This female is mosaic for Turner syndrome. She has a normal female
complement in only 2 of the 20 cells analyzed.

72

Autosomal recessive
connective tissue disorder
hyperflexibility, bruising
TNXB mutation leads to Tenascin X deficiency

Ehler Danlos

73

X-linked RECESSIVE
dystrophin disorder
progressive muscle weakness and wasting
cardiomyopathy in 2nd, 3rd decade
diagnostic is dec creatine kinase in blood (proportional to muscle mass)

Duchenne MD
(Becker=less severe form)

74

Two examples of uniparental disomy (UPD), where both homologs from 1 parent (nondisjunction error)

Prader Willi
Angelman

75

most common familial inherited neuropathy
familial/inherited
demyelinating peripheral neuropathy
17 dup

S/Sx:
sensory loss, ataxia, tripping, ankle strains, high arch, distal muscular atrophy, wasting

no cure, PT, orthopedic surgery, orthotics to maintain gait/balance

Charcot Marie Tooth (CMT)

76

elfin face
stellate iris
hypercalcemia
friendly social personality
hoarse voice
supravalvular aortic stenosis
7 deletion

Williams

77

prominent nose
congenital heart defects
cleft palate
hypocalcemia
immune def
learning difficulty
22 deletion

CATCH 22
Cardiac (supravalvular aortic stenosis)
Abnormal face (elfin face)
Thymic hypoplasia
Cleft palate
Hypocalcemia

DiGeorge/VCFS

detected by FISH

78

AUTOSOMAL RECESSIVE (need 2 alleles to express)
confers malarial resistance
8% of african americans
ALL SOMATIC CELLS AFFECTED-->painful episodes

Cause:
single point mutation in beta chain
Glu-->Val
HbS decreased solubility when deox (under hypoxic conditions)

S/Sx:
Anemia d/t dec NO and reduced RBC lifespan
vasocclusive crisis-->ischemia
stroke in peds
hemorrhagic in adults
ACS (acute chest syndrome): chest pain, fever, hypoxia, pulm infiltrates
retinopathy
cholelithiasis (gallstones)
Priapism (sustained painful erection, req aspiration)
pulmonary hypertension
CKD (chronic kidney damage)
splenic infarction (sepsis risk)

Tx:
cured by bone marrow stem cell transplant, $
RBC transfusion, but iron overloading
oral, IV narcotic analgesia
Hydroxyurea, increase HbF, compliance issues
prophylactic antibiotics to prevent SPLENIC infarction

Sickle Cell Anemia

79

T/F: patients with sickle cell trait have sickle cell disease

False
carriers can have sickle cell trait

80

Causes:
47, +18
d/t meiosis I (maternal) nondisjunction, meiosis II nondisjunction, or AMA

partial trisomy can also occur through translocation

S/Sx:
prenatal growth deficiency
small palpebral fissures (eye openings)
small mouth
low set ears
micrognathia
overlapping fingers, clenched hand
rocker bottom feet (convex)
club foot
Ventricular Septal defect
profound dev delays

Dx:
ultrasound: increased nuchal translucency (inc amniotic fluid)

Tx: symptomatic


Trisomy 18/Edwards

81

Primary Hyperoxaluria Type 2 caused by

Loss of organelle-targetting sequence

82

hematopoietic stem-cell disorder
9:22 Philadelphia chromosome translocation
Bcr-Abl oncoprotein
higher protein-tyrosine kinase activity

Tx: Imatinib (Gleevec), blocks myeloblast growth

CML
(Chronic Myeloid Leukemia)

83

Cl- ion transmembrane conductance regulator defect
Phenylalanine deletion

Sx: chest infections, mucus accumulation, shortness of breath

Dx: positive sweat test

CFTR

84

elevated creatine kinase in blood diagnostic of

MI

85

exposure to nitrates inhibits methemoglobin reductase, causing irreversible O2 binding to oxidized Fe3+ leading to

methemoglobinemia
Sx: cyanotic, brownish chocolate colored skin, hypoxemia

86

single point mutation that causes SCA changes AA from ___ to ___

Glu-->Val

87

T/F: RBCs of patients with sickle cell trait have a tendency to assemble into strands, causing vasoocclusion

False,
sickle cell trait =/ sickle cell disease

88

Sickle cell polymerization is (reversible or irreversible)

irreversible

89

CGG repeat
Materal expansion
no anticipation (exception)
long face, post-pubertal macroorchidism (enlarged testes), long face, large jaw, large ears, autism, mitral valve prolapse

mechanism:
CGG repeat
Hypermethylation of FMRP 5' UTR
Loss of FMRP protein
increased glutamate receptors

Xtra large testes, jaw, ears

Fragile X

90

CAG repeat
translated into polyglutamine repeats
mutated _______ protein
Neuronal loss (striatal neurons)
earlier onset=more severe
Paternal expansion

S/Sx:
facial chorea, dystonia (involuntary movement), bradykinesia (slow movement asi parkinsons), executive dysfunction, aggression, depression, dementia,

Huntington's
Hunting 4 CAGs
(Chrom 4)
mutated Huntington protein

91

Triple repeat diseases and their associated trinucleotide repeat
(use mnemonic)

Huntington's
Myotonic Dystrophy Type 1
Friedreich's Ataxia
Fragile X Syndrome
Spinal-Bulbar Muscular Atrophy (Kennedy's)

(middle letter)
X-Girlfriend's First Aid Helped Ace My Test
(X=CGG)
(Friedreich's = GAA)
(Huntington's = CAG)
(Myotonic = CTG)

92

Hallmark of triple repeat diseases

Anticipation
(earlier occurrence and increased severity of disease d't increased # of repeats in subsequent gen)

Note: most repeat diseases follow DOMINANT inheritance pattern

93

CTG repeat
delayed release of handgrip (myotonia)
muscle wasting, cataracts, testicular atrophy, frontal balding, arrythmia

Autosomal DOMINANT

My Tonia
My Testicles (testicular atrophy)
My Toupee (frontal balding)
My Ticker (arrhythmia)

Myotonic Dystrophy

94

GAA repeat
GAA
Gait Affected AR (autosomal recessive)
Ataxia (loss of bodily movement control)
Hypertrophic Cardiomyopathy
Scoliosis

Friedreich's Ataxia

GAAR (Gait Affected autosomal Recessive)

Friedreich
Frequent falls (ataxia)
RECESSIVE
(i)
(e)
Dorsal Column (vibratory, proprioceptium)
Recessive
(e)
(i)
Cerebellar involuntary-->nystagmus
Hypertrophic cardiomyopathy
Scoliosis

95

69, XXY
69, XXX
69, XYY
miscarriage
majority diandric
S/Sx = *macrocephaly, syndactyly*

Triploidy

S/Sx:
severe *macrocephaly, syndactyly*

96

Small distal segments in this type of translocation: risk of liveborn with this type of translocation

Large distal segments in this type of translocation: large risk of miscarriage

Unbalanced

97

Dicentric and Acentric chromosomes can occur in this type of inversion --> no viable zygotes

ParAcentric

98

Partial Monosomy and Trisomy with 1 centromere can occur in this type of inversion -->more viable offspring but with complications

PerIcentric

99

name the 2 trinucleotide repeat diseases involving DNA

Fragile X, Friedreich's Ataxia

100

name 5 trinucleotide repeat diseases involving RNA

Myotonic Dystrophy, ALS, Huntington's, Fragile X, Fuch's

101

caused by CTG repeats in DMPK gene

Myotonic Dystrophy Type 1

102

caused by CCTG repeats

Myotonic Dystrophy Type 2

103

T/F: earlier onset of CTG repeats is less severe for Myotonic Dystrophy

False! More severe with earlier age (ANTICIPATION=earlier occurrence and increasing severity)

104

mechanism:
CTG repeats
CTG repeats transcribed into RNA (3' UTR) as CUG repeats
sequestration (loss) of MBNL proteins

S/Sx:
christmas tree cataracts
myotonia

Myotonic Dystrophy Type 1

105

CUG repeats can produce disease phenotype in what disease (hint: usually CTG repeats)

Muscleblind MBNL proteins bind repeats
MBNL proteins regulate ALTERNATIVE SPLICING
Loss of MBNL 1--> cataracts, myotonia

Myotonic Dystrophy

106

G4C2 antisense
RNA foci
RAN translation

ALS

107

most repeat expansion diseases are _______ but Friedreich's Ataxia is ________

dominant, recessive

108

autosomal recessive
low PAH
inability to metabolize phenylalanine

S/Sx: mental retardation

Dx: PAH screening tests, 2nd test to confirm Dx

PKU

109

one gene and one type of mutation leads to disease in all individuals (100% penetrance)

Huntingtons

110

one gene and one mutation but DIFFERENT gene and mutations in different individuals leads to...

Retinitis Pigmentosa

111

T/F: Trisomies 18 and 21 exhibit 100% penetrance

True

112

should you screen for BRCA1/2 in the general population?

No. BRCA1/2 mutations are rare in the general population. only screen if individual or family history suggests

113

family with history of breast cancer, person has one BRCA allele. Relative risk is

very high

114

Diseases prevalent in Ashkenazi Jew population (d/t) FOUNDER EFFECT

Tay Sachs, Breast Cancer, Bloom's, Niemann-Pick Type A, Gaucher Type 1, Familial Dysautonomia, Fanconi Anemia Type C, Mucolipidosis IV, Cystic Fibrosis

115

Diseases prevalent in Ashkenazi Jew population (d/t) isolation (founder effect)

Alzheimers, Parkinsons, diabetes, Tay Sachs

116

Diseases prevalent in Icelandic population:

coronary heart disease, osteoporosis, Type II Diabetes, stroke

117

Diseases prevalent in Cajun population:

Friedreich's Ataxia, Charcot-Marie-Tooth, Retinitis Pigmentosa, Alstrom, Usher, Tay Sachs, Niemann-Pick

118

Asthma. mendelian or polygenic?

polygenic
at least 3 genes in oxidative stress pathway

119

which Apolipoprotein poses increased risk for Alzheimer's

ApoE4

120

T/F: APOE4 has been shown to pose increased risk for Alzheimer's, so we should test patients for APOE4.

False. ApoE4 tests not suggested as a diagnostic tool. it may tell you you're more likely to get it, but not "how much"...so not very useful

121

Alzheimer's can only be definitively diagnosed by...

brain autopsy for plaques and tangles

122

in the absence of ____ protein, HIV mRNA is retained in the nucleus and cannot be translated

Rev

123

siRNAs target the ____ gene in HIV, preventing ____ gene transcription into ____protein, an essential transactivating protein that allows viral HIV mRNA to be translocated to the cytoplasm for translation of viral proteins
(same answer)

Rev

124

siRNAs target oncogenic genes such as those encoding ______ in human pancreatic carcinoma

K-Ras

125

Respiratory diseases such as Asthma and CF lead to chronic inflammation. siRNA reduces _______ levels, thereby reducing inflammation

interferon

126

this disease results from a mutation in the SLITRK1 gene that produces/creates a binding site for miRNA

Tourette's
miRNA mediated downregulation of SLITRK1 d/t SLITRK1 mutation

127

disease caused by random point mutation in SLITRK1 gene (promotes dentritic growth) producing a novel miRNA binding site, leading to downregulation of SLITRK1 and hence, dendritic growth failure

Tourette's

128

Myostatin protein inhibits muscle growth
Myostatin ______ results in exceptionally meaty animals (increased muscle mass)
(ex: Belgian Blue Cattle, Mighty Mouse, Whippets dogs)

knockdown
ie DEFICIENCY

129

This kind of therapy would help patients with muscular dystrophy or other muscle wasting diseases

Myostatin (inhibits muscle growth) knockdown
(knockdown the growth inhibitor-->growth)

130

myostatin levels are lower in Texel sheep due to mutation that causes a _______ binding site

miRNA

131

mutation in DICER causes loss of DICER causes loss of mature miRNA and inadequate downregulation
this mechanism applies to what disease, promoting mesenchymal proliferation

Familial Pleuropulmonary Blastoma (PPB)

132

mutation in the mRNA itself causes

cancer. Chronic Lymphoid Leukemia

133

disease caused by random point mutation in SLITRK1 gene (promotes dentritic growth) producing a novel miRNA binding site, leading to downregulation of SLITRK1 and hence, dendritic growth failure
overlapping of Neocortex and Hippocampus

Tourettes

134

mutation that creates an miRNA binding site causes

Tourettes

135

most breast cancer is (sporadic, hereditary, familial)

sporadic

136

Mutations in BRCA1/2 are the most common causes of ______ breast and ovarian cancer

hereditary

137

moderate risk gene for HEREDITARY breast cancer

Chek2

138

new-risk gene for HEREDITARY breast cancer

NBN

139

hereditary breast and ovarian cancer (HBOC) follows a _____ inheritance pattern

autosomal Dominant

140

BRCA1/2 causes increased risk of what 5 cancers?

Breast, Ovarian, Pancreatic, Prostate, Melanoma (Derm)

141

Hereditary Breast and Ovarian Cancer is
a. mendelian, mutation at single gene locus BRCA1 causes cancer
b. polygenic, encompassing many high risk, moderate risk, and new risk genes

b.

142

A heterozygous mutation in new risk gene NBM causes

Nijmegen Breakage Syndrome

S/Sx: microcephaly, short stature, respiratory tract infections d/t immunodeficiency, intellectual disability,

increased risk of Non-Hodgkin Lymphoma (50% develop), Melanoma, Breast Cancer

143

moderate risk gene Chek2 follows _______ inheritance pattern

autosomal Dominant

144

increased cancer risk from Chek2

Breast, Ovarian, Colon, Prostate, Thyroid, Endometrial

145

abnormal fetal position and diminished fetal movement are examples of birth _____

deformation

146

gastroschisis is an example of (deformation, disruption, malformation)

disruption

147

cleft lip and trisomy 13 are examples of (deformation, disruption, malformation)

malformation

148

most cases of Down Syndrome (trisomy 21) result from _____, followed by ______, followed by _______

nondisjunction (95%)
14:21 translocation (4%)
mosaicism (1%)

149

S/Sx:
micrognathia, cleft palate, upward positioning of tongue, interference w/ palate closure, airway obstruction
most cases Non-Syndromic

Pierre Robin SEQUENCE

150

decreased amniotic fluid
fetal constraint-->arthrogryposis (joint contracture), intraorbital folds, micrognathia, low set ears

decreased lung fluid-->pulmonary hypoplasia (under cell growth/underdevelopment)-->respiratory failure

Oligohydramnios AKA Potter SEQUENCE

151

S/Sx:
Cystic hygroma (nuchal/neck swelling)
Webbed neck

Jugular Lymphatic Obstruction SEQUENCE

152

S/Sx:
Bladder distension-->hydroureter, renal dysplasia-->abdominal muscle deficiency-->excess abdominal skin (pruning

Urethral Obstruction SEQUENCE (Prune Belly)

153

S/Sx:
single upper incisor
cleft lip/palate
midface malformations
fused forebrain

Holoprosencephaly SEQUENCE

154

Vertebral
Anal atresia/stenosis (narrowing)
Cardiac: VSD
Tracheo-Esophageal fistula (passage b/t 2 hollow organs)
Renal
Limb (polydactyly, syndactyly)

VACTERL

155

increased distance b/t orbits

Hypertelorism

156

decreased distance b/t orbits

Hypotelorism

157

increased opening b/t eyelids

wide palpebral fissures

158

decreased opening b/t eyelids

short palpebral fissures

159

condition where lateral canthus slants downwards

down-slanting palpebral fissures

160

condition where lateral canthus slants upwards

up-slanting palpebral fissures

161

embryonic deficiency of 1st, 2nd pharyngeal arches
autosomal dominant
facial dysmorphism
micrognathia, zygomatic (zygomatic arch=bony arch of cheekbone) hypoplasia, atresia of middle ear, hearing loss, down-slanting palpebral fissures, lower eyelid coloboma (hole in eye structure)
NORMAL IQ

Treacher Collins syndrome
NORMAL IQ!

162

characteristic facial dysmorphism
short palpebral fissures
flat philtrum, thin upper lip
mid-face hypoplasia

Fetal Alcohol Syndrome

163

RET oncogene mutation in MEN1/2 is a (somatic, germline) mutation

germline

164

mycN gene amplification involved in

Neuroblastoma, Prostate Cancer

165

fill in the blank. RAS = a family of ____________

proto-oncogenes!

166

Treatment for disease caused by Philadelphia chromosome 22:9 translocation

Gleevec (imatinib), Tyrosine Kinase inhibitor, CML treatment

167

oncogenic mutations are usually somatic, but can sometimes be germline. what is the prime example of an oncogenic germline mutation?

germline mutation in RET, causes MEN1, MEN2

168

HRAS hypomethylation would lead to HRAS _____, asi ______ cancer

activation, colon

169

liver cancers tend to have elevated ______ protein, a ______ factor

hnRNP2, splicing

170

men with breast cancer may harbor a mutation in what gene?

BRCA2

171

dominant
tumor suppressor loss of function
neurofibromin protein normally inhibits RAS
dec neurofibromin, RAS activation-->proliferation
FULL PENETRANCE
variable expressivity

S/Sx:
benign Schwann cell tumors on nerve endings (skin)
plexiform neurofibromas/neuroma (Schwann cells proliferate inside nerve sheath) may transform into malignant peripheral nerve sheath tumors
Cafe-au-lait spots (cafe con leche)

NF1
Neurofibromatosis

172

inherited germline APC tumor suppressor loss of function mutation
each polyp is result of independent 2nd hit

Familial Adenomatous Polyposis (FAP, colorectal cancer)

173

mutation in mismatch repair genes known as MUTATOR genes
NOVEL alleles due to inability to repair mismatches
loss of 2nd allele-->tumorigenesis
microsatellite instability

no early presence of polyps
increased risk for other cancers

Hereditary non-polyposis colon cancer (HNPCC aka Lynch Syndrome, colorectal cancer)

174

HNPCC is also known as

Lynch

175

as seen in HNPCC, a mutation in mutator (mismatch repair) genes leads to _______ alleles

novel

176

microsatellite instability, as seen in HNPCC (Lynch), indicates loss of ________ gene

mutator (mismatch repair)
also: novel alleles present when mutator gene lost

177

causative gene for Alveolar Capillary Dysplasia (ACD)

FoxF1

178

30-40% of cases have FoxF1 mutation, very small microdeletion.
100% penetrance, variable expressivity
DOMINANT FoxF1 mutation-->loss of 1 copy=disease phenotype
in ACS FoxF1 cases, FoxF1 de novo microdeletion
also FoxC2 loss
some cases autosomal RECESSIVE inheritance (25% risk)
pulmonary vasculature anomaly
alveolar-capillary membrane not formed (air-blood GAS o2 for co2 diffusion membrane) not formed
"misalignment" of pulmonary veins

S/Sx:
severe hypoxemia
pulmonary hypertension
ass. anomalies: cardio, gastro, uro, musculoskeletal

Dx:
lung biopsy or autopsy


Alveolar Capillary Dysplasia

179

ATM gene mutation yields increased risk for _____ and _______ cancers

breast, colorectal

180

CHEK2 gene mutation yields increased risk for _____ and _______ cancers

breast, colon