Friggin' Genetic Disorders Flashcards
1
Q
What chromosome is affected in CF?
A
7q31.2
2
Q
symptoms of CF
A
lung disease, pancreatic insufficiency, steatorrhea, intestinnal obatruction, male infertility
3
Q
what population is affected by cf
A
caucasians
4
Q
What population is affected by PKU
A
caucasians, from scandinavian descent, not AA or jewish
5
Q
What are characteristic symptoms are found in patients with PKU
A
mousy/musty odor in urine
severe mental retardation and hypopigmentation hair and skin, eczema
6
Q
What enzyme is affected in phenylketonuria
A
phenylalanine hydroxylase
7
Q
What enzyme is affected in tay sachs disease
A
hexoadminidase
8
Q
What diseases are Autosomal dominant
A
huntington disease, Marfan syndrome
9
Q
Autosomal recessive diseases
A
CF, sickle cell disease
10
Q
X linked recessive diseases
A
hemophilia, Fabry disease
11
Q
X linked dominant disease
A
fragile X syndrome
12
Q
codominant eamples
A
ABO blood group, alpha -1 antitrypsin deficiency
13
Q
Mitochondrial inheritance disease example
A
Leber hereditary optic neuropathy
14
Q
What enzyme is affected in galactosemia
A
Galactose 1 phosphate uridyltransferase def
15
Q
What happens in alpha 1 antitrypsin deficiency
A
unable to inactivate neutrophil elastase in lung, leads to emphysema from a failre to inactivate a tissue damaging substrate
16
Q
What is the disease mechanism in Familial hypercholesterolemia
A
decreased synthesis/function of LDL receptor
17
Q
What is the structure alteration in Thalassemias
A
mutation in globin gene affects amount of globin chains synthesized
18
Q
What is affected by antimalarial primaquine
A
G6PD, leads to severe hemolytic anemia
19
Q
What chromosomes are affected in Marfan syndrome
A
15Q21.1
5Q23.31 (less so)
20
Q
What genes are affected in Marfan syndrome
A
FBN1
FBN2 (less so)
21
Q
What is the mechanism of Marfans’ syndrome
A
loss of fibrillin leads to loss of structural support in microfibril rich connective tissue, and TGF-B is activated excessively
22
Q
What syndrome tends to have subluxation/dislocation of the lens?
A
Marfan syndrome
23
Q
What is the mechanism of EDS
A
defect in synthesis/structure of fibrillar collagen
24
Q
What is a unique feature of EDS compared to Marfans
A
Skin is stretchable, fragile, and vulnerable to trauma. Leads to internal complications such of rupture of colon and large arteries.
25
Class I/II inheritance pattern
autosomal dominant
26
Classic I/II clinical findings
skin and joint hypermobility, atrophic scars, easy bruising
27
Classic I/II Gene defects
COL5A1, COL5A2
28
Vascular (IV) clinical findings
thin skin, arterial/uterine rupture, bruising, small joint hyperextensibility
29
Vascular IV inheritance pattern
Autosomal dominant
30
Vascular IV gene defects
COL3A1
31
Kyphoscoliosis VI clinical findings
hypotonia, joint laxity, congenital scoliosis, ocular fragility
32
Kyphoscoliosis VI inheritance pattern
Autosomal recessive
33
Kyphoscoliosis VI gene defects
Lysyl hydroxylase
34
Clinical finding in familial hypercholesterolemia
Tendinous xanthomas, increased plasma cholesterol levels, increased risk of MI
35
What is primary accumulation in lysosomal storage Dzs
catabolism of substrate of missing enzyme is incomplete, so it accumulates within the lysosome
36
What are the 2 general approaches to treat lysosomal storage diseases
Enzyme replacement therapy
| Substrate reduction therapy
37
What is the most common form of GM2 gangliosidosis
Tay Sachs disease
38
What chromosome is affected in tay sachs disease
Chr 15, in alpha subunit locus.
39
What does Tay Sachs disease manifest with
severe deficiency of hexosaminidase A
40
What population is affected in Tay Sachs disease
Ashkenazi Jews (Eastern european)
41
What are the clinical manifestations of Tay SWachs disease
cherry red spot in macula
6 mo motor and mental deterioration, obtunded, flaccidity, blindness and dementia
1-2 yo vegetative state, 2-3 death
42
Where does GM2 ganglioside accumulate
neurons, retina, heart, liver, spleen
43
What tests determine if GM2 ganglioside accumulations are present
fat stains oil red O
| Sudan black B positive
44
What causes Niemann-Pick DZ
lysosomal accumulation of sphingomyelin due to inherited deficiency of sphingomyelinase
45
What population is affected by Niemann Pick DZ
Ashkenazi Jews, AR
46
What chr is affected in Niemann Pick DZ
Chr 11p15.4 (expressed more on maternal part)
47
What is the most severe form of Niemann Pick DZ
Type A, severe infantile form.
48
Clinical manifestations of Niemann Pick DZ type A
extensive neuro involvement, mkd visceral accumulations of sphingomyeline, progressive wasted, symptoms by 6mo, death b4 3 yo
49
Clinical manifestations of Niemann Pick DZ type B
organomegaly, No CNS involvement, reach adulthood
50
Clinical manifestation of Niemann Pick DZ type C
Most common, affects NPC1. Progressive neurological damage, ataxia, vertical supranuclear gaze palsy, dystonia, dysarthria, psychomotor regression
51
Morphology of Niemann Pick DZ (histo)
zebra bodies, massive splenomegaly,
52
Gaucher Dz affects
glucocerebrosidase mutation
53
Etiology of Gaucher DZ
accumulation of glucocerebroside, activation of macrophages so that IL-1, IL-6 and TNF are released
54
What are the manifestations of Type 1 gaucher dz
No CNS involvement, spleen and bone sx, slt & slt life span
55
What population is affected in Type IGaucher DZ
European Jews
56
Clinical manifestations of Type II lysosomal storage
infantile cerebral pattern, progressive CNS invovlement, early death, hepatosplenomegaly
57
What population is affected in Type II gaucher DZ
Not jewish europeans
58
Clinical manifestations of Type III Gaucher DZ
systemic involvement with progressive DNZ dz, begins in adolescence/early adulthood
59
Morphology of Gaucher DZ
distended phagocytic cells in liver/spleen or BM, which leads to bone erosion, typically see cells that look like crumpled tissue paper.
Spleen is huge.
60
Treatement of Gaucher DZ
allogeneic hematopoietic stem cell transplant; recombinant enzyme replacement
61
What is affected in Mucopolysaccharidoses
enzymes degrading glgycosaminoglycans are deficient
62
Inheritance pattern of MPS
autosomal recessive, except Hunter, which is X linked recessive
63
Clinical manifestations of MPS
coarse facial features, clouding of the cornea, joint stiffness, mental retardation
64
Clinical manifestation of Hurler syndrome
hepatosplenomegaly by 6-24 mo, death 6-10 yo, cardiovascular complications, growth retardation, coarse facial features, skeletal abn
65
Clinical manifestation of Hunter syndrome
MPS II, No corneal clouding, milder clinical course
66
Morphology of MPS
in mononuclear phagocytic cells, endothelial cells, have balloon cells that have a clear cytoplasm and multiple vacuoles with swollen lysomsomes. Lamellated zegra bodies.
67
Enzyme deficiency in Von Gierke
glucose 6 phosphatase
68
Clinical features of Von Gierke
failure to thrive, hepatomegaly, renomegaly, hypoglycemia, hyperlipidemia, bleeding tendency
69
Pompe disease enzyme deficiency
lysosomal acid maltase
70
clinical features of pompe disease
massive cardiomegaly, muscle hypotonia, cardiorespiratory failure
71
Enzyme deficiency in McArdle dz
muscle phosphorylase
72
Clinical manifestation of McArdle
cramps after exercise, no increased blood lactate after exercise
73
Morphology of pompe dz
glycogen filled myocardial cells
74
What is an example of multifactorial inheritance?
cleft lip, cleft palate, and neural tube defects
75
What is a ring chromosome
break of chr occurs at both ends of the chr, with fusion of the damaged ends.
76
What is paracentric inversion
inversion involving only one arm of the chromosome
77
What is pericentric inversion
breaks are on opposite sides of centromere
78
What is isochromosome
When one arm of the chromosome is lost, so the remaining arm is duplicated. Means you have two short arms only or two long arms only.
79
What is robertsonian translocation
translocation between 2 acrocentric chromosome, breaks are closer to the centromeres of each chromosome.
80
What is Trisomy 21 generally caused by
robertsonian translocation
81
What influences trisomy 21
Robertsonian translocation
| Maternal age
82
What are the clinical manifestations of trisomy 21
flat facial profile, oblique palepebral fissures, epicanthic folds. IQ of 25-50. Congenital heart disease, and have an increased risk of developing acute leukemia.
83
What kind of immune response do patients with trisomy 21 have
abnormal one, predisposes them to serious infections of lungs and thyWroid autoimmunity
84
What chromosome is affected in Edward's syndrome
18
85
Clinical manifestations of Edwards syndrome
low set ears, overlapping fingers, congenital heart defects, micrognathia, prominent occiput
86
What chromosome is affected in Patau's syndrome
13
87
Clinical manifestations of Patau's syndrome
Microphthalmia, polydactyly, microcephaly, cleft lip and palate, renal defects
88
What chromosomal deletion can lead to DiGeorge Syndrome and Velocardiofacial syndrome
22q11.2
89
Clinical manifestations of DiGeorge syndrome
thymic hypoplasia, T cell immunodeficiency, parathyroid hypoplasia (leads to hypocalcemia, cardia malformations and mild facial anomalies)
90
Clinical manifestations of Velocardial syndrome
facial dymorphism, prominent nose, cleft palate, cardiiovascular anomalies and learning disabilities
91
What is CATCH 22 for DiGeorge syndrome
```
Cardiac abnormality
abnormal facies
thymic aplasia
cleft palate
hypocalcemia
```
92
What is lyonization
X chromosome is compacted to make a Barr Body, which makes it inactive.
93
What increases the likelihood of mental retardation
of X chromosomes
94
Chromosomal abnormalities associated with Klinfelter syndrome
XXY
95
Clinical manifestations of Klinefelter syndrome
eunuchoid body habitus with long legs, small atrophic testes and small penis, gynecomastia, lower IQ.
Increased risk of Type 2 DM and metabolic syndrome, mitral valve prolapse. Leads to male infertility and increased risk of breast cancer.
96
Chromosomal abnormality of Turner syndrome
complete/partial monosomy of X chr.
97
Clinical manifestations of turner syndrome
cystic hygroma, swelling of nape of neck due to lymph stasis. congenital heart disease, cardiovascular abnormalities, short stature, cubitus valgus, amenorrhea, hypothyroidism, glucose intolerance, obesity and insulin resistance.
98
What kind of ovaries are found in patients with Turner syndrome
Fibrotic ovaries
99
What gene and locus are affected in Fragile X syndrome
FMRI and X27.3
100
What gene and locus are affected in Huntington disease
HTT and 4p16.3
101
What trinucleotide repeat is in Fragile X syndrome
CGG
102
What trinucleotide repeat is in Huntington disease
CAG
103
What is a morphological hallmark of trinucleotide repeat mutations
accumulation of aggregated mutant proteins in large intranuclear inclusions
104
Clinical manifestations of Fragile X syndrome
```
long face with a large mandible
large everted ears
large testicles
hyperextensible joints
high arched palate
mitral valve prolapse
```
105
What is anticipation
clinical features of fragile X syndrome worsen with each successive generation, and mutation becomes worse with each generation as it is passed on.
106
What defines carrier males of Fragile X syndrome
20% of males who carry Fragile X mutation but are clinically and cytogenetically normal. Transmit trait through all phenotypically normal daughters to affected grandchildren.
107
How many females are affected in fragile X syndrome
30-50 percent of carrier females are affected.
108
What is huntington's disease characterized by
autosomal dominant disease, that has progressive movement disorders/dementia.
109
What is huntington's disease caused by
degeneration of striatal neurons. Fro polyglutamine trinucleotide repeat expansion disease.
110
What is the threshold effect
minimum number of mutant mtDNA that must be present in a cell/tissue before oxidative dysfunction gives rise to disease
111
What is an example of a mitochondrial gene disorder
Leber hereditary optic neuropathy
112
Clinical manifestations of Leber hereditary optic neuropathy
bilateral loss of central vision, started between ages 15 and 35. Leads to eventual blindness. Cardiac conduction and minor neurologic manifestations may also occur.
113
What is the chromosomal abnormality of Prader-Willi syndrome
Imprinting of paternal allele. Interstitial deletion of band q12 in long arm of chromosome 15.
114
Chromosomal abnormality of Angelman Syndrome
Imprinting of maternal allele
115
Clinical manifestations of Prader-Willi syndrome
mental retardation, short stature, hypotonia, profound hyperphagia, obesity, small hands and feet, hypogonadism
116
Clinical manifestations of Angelman syndrome
mentally retarded, ataxic gait, seizures, and inappropriate laughter. Happy puppets.
