FMS Week 3 Flashcards
1
Q
congenital cytomegalovirus infection
A
SNHL, chorioretinitis, microcephaly, ID
2
Q
inheritance characteristics of Fragile-X
A
most penetrant in males (only one X), female heterozygotes may have ovarian failure and ataxia, typically X-dominant
3
Q
general mechanism of FMR1 silencing
A
mutation leads to hypermethylation, silencing by HDACS, condensation of promoter
4
Q
situs ambiguous
A
mixed laterality or body patterning
5
Q
signs/symptoms of Angelman syndrome
A
ID/limited speech, ataxic gait, spontaneously happy affect, seizures
6
Q
thalidomide
A
sleep and anti-nausea med used during pregnancy
7
Q
phenotypic heterogeniety
A
multiple distinct phenotypes arising from different mutations in the same gene
8
Q
general indications for ACE inhibitors
A
hypertension
9
Q
what is the greatest cause of genetic disease?
A
multifactorial disorders
10
Q
inheritance of myotonic dystrophy
A
autosomal dominant
11
Q
teratogenic effects of anticonvulsants
A
nail hypoplasia (phenytoin), neural tube defects (valproic acid and carbamazepine)
12
Q
pathogenesis of type one DM
A
autoimmune destruction of the beta cells of the pancreas
13
Q
HOX genes
A
regional selection of patterning of body from hindbrain to tail
14
Q
heterotopias
A
apparently normal neurons in abnormal locations
15
Q
what type of condition is associated with LIS1?
A
neuronal migration: periventricular nodular heterotopia
16
Q
cause of Fragile X syndrome
A
CCG triplet expansion in FMR1 region of X-chromosome
17
Q
general anomalies associated with 2nd and 3rd trimester?
A
IQ, developmental problems
18
Q
best potential vector for SCIDs?
A
lentiviral
19
Q
teratogenic effects of tobacco
A
poor fetal growth, behavioral teratogenicity, IQ?
20
Q
what type of condition is associated with FLNA?
A
neuronal migration: periventricular nodular heterotopia
21
Q
teratogenic effects of Isotretinoin
A
CNS, cardiac, ear, thymic, branchial arch anomalies
22
Q
MELAS
A
mitochondrial disease: mitochondrial encephalopathy lactic acidosis and stroke-like episodes
23
Q
cause of Angelman Syndrome
A
“silencing” of maternal genes at 15q
24
Q
signs/symptoms of Fragile-X
A
15-20% have developmental delay, characteristic facial features (large forhead, long face, prominent chin/ears), joint laxity, enlarged testes in adults, associated with autism
25
general anomalies associated with 1st trimester?
congenital malformations
26
general indications for methotrexate/misoprostol
cancers, dermatomyositis
27
teratogenic effects of maternal PKU
microcephaly, ID, cardiac defects, pregnancy loss
28
Syndrome vs Sequence vs Anomaly
Syndrome: a pattern of anomalies known or thought to be related to a gene or teratogen
Sequence: one or more secondary morphologic anomalies cascading from a single malformation, disruption, or deformation
Anomaly: an anatomic phenotype substantially departing from reference population
29
what is the surmised mechanism of uniparental disomy?
trisomy rescue (trisomy with loss of second parent's chromosome around fertilization)
30
temporal colinearity
3' HOX genes expressed earliest
31
Waardenburg Type 1
mutation in PAX3, results in hypertelorism, white furlock, deafness
32
treatments for mitochondrial disorders
No effective treatment; cofactors like coQ10, thiamine, vitamin E, and carnitine
33
cause of Prader-Willi syndrome
results from "silencing" of paternal genes at 15q
34
number of CAG repeats associated with inormal patient (nonHD)
<26
35
what is organogenesis?
2-9 weeks post conception; approximately the first trimester
36
cause of Friedreich Ataxia
nucleotide expansion mutation in FXN gene on chromosome 9, codes for Fraxatin which removes iron in the cytoplasm around mitochondria, leads to free radical damage to mitochondrial membrane
37
what are the disadvantages of Lentiviral vectors?
potential for activating oncogenesis, potential for insertional mutagenesis (non selective and contains its own promoter)
38
spina bifida
neural tube defect, failure of fusion of vertebral arch, typically in lumbar region, varying degrees of severity
39
Describe Sonic hedgehog syndrome
Mutation in SHH gene, Holoprosencephaly, clefting, malformed midline structures, (cyclopia, central incisor, absent frenulum etc)
40
what type of slippage would lead to trinucleotide expansion?
backward slippage
41
Waardenburg Type IV
Hirschsprung disease (aganglionic megacolon)
42
Describe Tuberous sclerosis
Disease associated with TSC1, TSC2 genes. Hamartomas, cardiac thabdomyomas, ungual fibromas, facial angiofibromas, ashleaf spots, and seizures.
43
teratogenic effects of gestational diabetes
("abundant fuel") macrosomia, high insulin levels, hypoglycemia, polycythemia, hypertrophic cardiomyopathy, microcolon
44
CFTR gene
associated with CF, membrane bound protein associated with Cl- channels
45
teratogenic effects of ACE inhibitors
renal failure, skull defects
46
what are the 2 most common congenital anomalies?
undescended testes and heart defects
47
CRISPR-Cas9 gene editing involves what repair mechanism?
homologous recombination
48
what is the role of PAX genes?
transcription regulators, initiate and orchestrate eye development
49
signs/symptoms of Prader-Willi syndrome
neonatal hypotonia & cryptorchidism, hypothalamic dysfunction: lack of satiety & obesity, hypogonadotropic hypogonadism, growth hormone deficiency: short stature & hypotonia, congnitive/behavioral impairment
50
teratogenic effects of thalidomide
stunted growth, phocomelia ("seal limbs")
51
what is "Anticipation"?
worsening of triplet repeats in subsequent generations
52
teratogenic effects of lithium
ebstein's anomaly of tricuspid valve
53
teratogenic effects of lead
impaired CNS function
54
antisense RNA therapy
oligoribonucleotides that pair to mRNA, can block translation/splicing
55
what tissues are most affected by mitochondrial diseases?
neuro, muscular, and cardiac
56
teratogenic effects of 1st trimester diabetes
(insulin dependent), cardiac/sacral defects, neural tube defects, pregnancy loss
57
number of CAG repeats associated with juvenile HD
60+
58
situs inversus
mirrored laterality or body patterning
59
general teratogenic effects of TORCH infections
IUGR, prematurity, hypo/hypertonia, seizures, microcephaly, hydrocephalus, chorioretinitis, cataracts, glaucoma, hearing loss, pneumonia, strucural cardio defects, hepatosplenomegaly, petechiae/purpura, rash, jaundice
60
teratogenic effects associated with methotrexate/misoprostol
multiple organ systems/structures, most within the 1st trimester
61
uniparental disomy
both members of a chromosome pair are inherited from one parent
62
MERRF
mitochondrial disease: myclonic epilepsy and ragged red fibers
63
teratogenic effects of cocaine
pregnancy loss, placental abruption, intrauterine growth retardation (IUGR), microcephaly
64
what are the disadvantages of Adenovirus vectors?
high immune response (because they are so infectious) and not stably integrated
65
gene associated with CF
CFTR, large gene, associated with thousands of mutations
66
heteroplasmy
When a cell contains multiple mitochondrial lines (mitochondrial "mosaicism")
67
teratogenic effects of methylmercury
microcephaly, ID, cerebral palsy, minamata disease
68
what is a gene vector?
an engineered piece of DNA derived from a naturally occurring human virus
69
teratogenic effects of ACE inhibitors
decreased renal blood flow, renal failure, hypotension, anuria, skull hypoplasia, morbidity
70
Causes of nucleotide repeat expansions
hypermethylated regions/stable hairpins, mistakes during replication/repair, unequal crossing over during meiosis (gene conversion)
71
qualitative traits vs quantitative traits
qualititative: traits either present or not
quantitative traits: measurable physiological/biochemical quantities
72
signs/symptoms of Friedreich Ataxia
muscle weakness in arms/legs, loss of coordination, vision/hearing/speech impairment, scoliosis, high plantar arches, diabetes, heart disorders
73
describe SCIDs
severe combined immunodeficiency; due to adenosine deaminase deficiency, leads to build up of doxyadenosine and S-adenosylhomocysteine which are toxic to immune cells
74
periventricular nodular heterotopia
involves clusters of neurons that never begin migration, involved in 15+ syndromes
75
what are the disadvantages of Adenovirus-associated vectors?
small payload, infected cells are recognized by immune system and compromised
76
signs/symptoms of Myotonic Dystrophy
myotonia and wasting of smooth/skeletal/cardiac muscles, cardiac conduction defects, hypersomnia, cognitive changes, dementia
77
teratogenic effects of Zika virus
severe microcephaly, neurological complications, eyes and ears
78
mechanism of defect in myotonic distrophy
regions are "decoys" for CUG RNA binding proteins for mRNA metabolism, build up of non-degraded DMPK transcripts
79
what tissues are most affected by HD?
brain and testes
80
small interference RNA
siRNA, essentially artificial microRNAs that can target mRNAs using the RISC pathway, can be sent into the cell in engineered liposomes
81
cause of Noonan syndrome
a syndrome that arises from mutations in various proteins/enzymes related to the RAS-MAPK pathway
82
types of "silencing" in Prader-Willi/Angelman syndromes
At 15q: deletion, UPD, repression from imprinting defect, UBE3 mutation in Angelman
83
CPEO
mitochondrial disease: chronic progressive external opthalmoplegia
84
signs of fetal alcohol symptom
growth deficiency, microcephaly, learning disability, mild/moderate ID, behavioral (ADHD, impulsiveness, poor memory, conduct disorder), characteristic facial features
85
most common mutation class in cystic fibrosis
F508del (phenylalanine deletion)
86
situs solitus
normal laterality or body patterning
87
what are the 2 types of RNA-based therapies?
antisense RNAs and RNA interference
88
factors affecting teratogenicity?
timing, dose, predisposition (metabolism, genetics, physiology)
89
congenital rubella syndrome
IUGR, microcephaly, cataracts, hearing loss, chorioretinitis, meningoencephalitis, ID
90
NARP
mitochondrial disease: neurogenic ataxia and retinitis pigmentosa
91
when is a fetus/embryo most sensitive to teratogens?
organogenesis
92
what is the difference between malformation, deformation, and disruption?
malformations are intrinsic abnormalities in programs driving development.
deformations are from extrinsic forces on otherwise normally developing tissues
disruptions are when normal tissues are subjected to a destructive problem causing breakdown or loss (vascular, infection, etc.)
93
describe WAGR
Aniridia-wilms tumor association
PAX-6 deletion leads to aniridia, WT1 gene leads to Wilms tumor
94
inheritance of Friedreich Ataxia
autosomal recessive (25% recurrence)
95
anencephaly
anterior neural tube defect, 2/3 are female, typically stillborn or death shortly after birth
96
Type 1 vs Type 2 myotonic dystrophy
type 1: expansion in 3' UTR of DMPK gene on chromosome 19q
type 2: expansion in zinc finger 9 (ZNF9) gene on chromosome 3
97
cause of Huntington Disease
CAG repeat expansion at HTT of 4p
98
what type of condition is associated with DCX?
neuronal migration: periventricular nodular heterotopia
99
spatial colinearity
3' HOX genes expressed more anteriorly
100
number of CAG repeats associated with adult onset HD
40-60
101
TORCH
```
Toxoplasmosis
Other (Varicella, syphilis, Zika)
Rubella
Cytomegalovirus
Herpes
```
102
FMRP
protein associated with FMR1 gene (fragile-X); participates in RNA transport/function in neural cells
103
origination of cleft lip/palate
failure of fusion of frontal process with maxillary process early on (35th day of gestation), most common in males
104
MHC locus
major genetic factor in type 1 diabetes
105
what are the potential issues with CRISPR-cas9 systems?
unintentional editing, unpredictable effects on progeny, designer medicine
106
most common anomaly of folic acid deficiency during pregnancy
NTD (reduced blood folate and elevated homocysteine)
107
characteristic trait of Van der Woude syndrome (VWS)
bilateral lower lip pits
