General genetics / metabolic 5 Flashcards
1
Q
Androgen insensitivity syndrome
features
gene(s)
inheritance
A
- feminization of external genitalia
- AR gene
- XL inheritance
2
Q
Thanatophoric dysplasia
features
gene(s)
inheritance
A
- perinatal lethal short-limb dwarfism syndrome
- FGFR3 gene
- AD inheritance
3
Q
Hirschsprung disease
features
gene(s)
inheritance
A
- complete absence of neuronal ganglion cells from a portion of the intestinal tract; leads to constipation
- varying underlying causes / inheritance patterns (T21, deletions, Bardet-Biedl, familial dysautonomia, Mowat-Wilson, MEN2, NF1, SLOS, Waardenburg, others)
4
Q
Cystic fibrosis
features
gene(s)
inheritance
A
- effects epithelia of the respiratory tract, exocrine pancreas, intestine, male genital tract, hepatobiliary system, exocrine sweat glands
- CFTR gene
- AR inheritance
5
Q
SMA
features
gene(s)
inheritance
A
- progressive muscle weakness resulting from degeneration of the anterior horn cells; onset between gestation and young adulthood
- SMN1 and SMN2 genes
- AR inheritance
6
Q
Klippel Trenaunay Weber
features
gene(s)
inheritance
A
- capillary malformations associated w/hypertrophy of bones and soft tissues
- unknown genes, sporadic
7
Q
Simpson Golabi Behmel
features
gene(s)
inheritance
A
- macrosomia, distinctive facies (coarse), ID
- GPC3, GPC4 genes
- XL inheritance
8
Q
Facioscapulohumeral muscular dystrophy
features
gene(s)
inheritance
A
- progressive muscle weakness presenting before age 20y
- DUX4 gene in D4Z4 repeat region (most have 1-10 repeats; normal is 11-100)
- AD inheritance
9
Q
Myotonic dystrophy, type 1
features
gene(s)
inheritance
A
- cataract, myotonia (sustained muscle contraction), cardiac conduction abnormalities
- CTG trinucleotide repeat expansion in DMPK
- AD inheritance
10
Q
X-linked ichthyosis / steroid sulfatase deficiency
features
gene(s)
inheritance
A
- dry and scaly skin, sparse hair, conical teeth
- deletion of STS gene on Xp
- XL inheritance
11
Q
Bardet Biedl
features
gene(s)
inheritance
A
- blindness by 15y; truncal obesity; postaxial polydactyly, LD/ID
- 18 genes (many start with “BBS”)
- AR inheritance
12
Q
Kearns-Sayre
features
gene(s)
inheritance
A
- various eye issues leading to ptosis and vision loss; cardiac conduction defects, ataxia
- mtDNA deletions
- rarely inherited
13
Q
Spinocerebellar ataxia
features
gene(s)
inheritance
A
- several types;
- various; repeat expansions
- various
14
Q
Kennedy disease
features
gene(s)
inheritance
A
- aka spinal and bulbar muscular atrophy
- gradually progressive degeneration of lower motor neurons; fasciculations; mild androgen insensitivity
- CAG repeat expansion in AR gene
- XL inheritance
15
Q
Friedreich’s ataxia
features
gene(s)
inheritance
A
- slowly progressive ataxia w/onset in teens; dysarthria, muscle weakness, scoliosis, absent lower limb reflexes; some w/cardiomyopathy
- FXN gene repeat expansion
- AR inheritance
16
Q
Alpha thalassemia
- types
- gene(s)
A
- Hb Bart
- hemoglobin H
- HBA1 and HBA2 genes
17
Q
Hb Bart
features
gene(s)
inheritance
A
- fetal onset of edema; severe anemia; various defects; death in neonatal period
- all 4 alpha-globin alleles deleted or inactivated
- AR inheritance
18
Q
Hemophilia A
features
gene(s)
inheritance
A
- bruising; bleeding (muscle, joint, soft tissue)
- F8 gene
- XL inheritance
19
Q
Hemophilia B
features
gene(s)
inheritance
A
- bruising; bleeding (muscle, joint, soft tissue)
- F9 gene
- XL inheritance
20
Q
Sickle cell anemia
features
gene(s)
inheritance
A
- intermittent vaso-occlusive events and chronic hemolytic anemia; pain/swelling in hands/feet of children often earliest manifestation
- HBB gene
- AR inheritance
21
Q
Von Willebrand features gene(s) inheritance incidence; penetrance
A
- mucosal membrane hemorrhage (mouth, nose, uterus)
- VWD gene
- AD inheritance more common, some AR
- incidence 1/100 w/very low penetrance
22
Q
SMA
subtypes
A
- 0: prenatal onset / severe
- 1: onset before 6m
- 2: onset 6-12m
- 3: onset in childhood after 1y; ability to walk 25 meters achieved
- 4: adult onset
23
Q
SMN1 and SMN2 genes
- types of mutations
- copy number
- -SMN1
- -SMN2
A
- almost identical; SMN 2 lacks the SMN1 exon 7
- 95% of affecteds are homozygous for deletion or gene conversion (SMN1->2) as opposed to having one intragenic mutation
- SMN1 copy number: 5-8% of people have 2 copies on a single chromosome
- SMN2 copy number: 3+ copies correlated to milder phenotype
24
Q
DRPLA
features
gene(s)
inheritance
A
- progressive brain disorder causing involuntary movements, mental/emotional problems; onset ~30y
- ATN1 gene
- AD inheritance
25
Which factors are associated with hemophilia A and B?
Factor VIII: hemophilia A
| Factor IX: hemophilia B
26
Is hemophilia A or B more common?
A; but they are clinically indistinguishable
27
Are there promoter mutations which cause hemophilia A or B?
only B
28
HbH disease
features
gene(s)
inheritance
- microcytic hypochromic hemolytic anemia; mild jaundice; bone changes; hepatosplenomegaly
- deletion or dysfunction of 3 of 4 alpha-globin alleles
- AR inheritance
29
Beta-thalassemia
features
gene(s)
inheritance
- microcytic hypochromic anemia; hepatosplenomegalia; FTT
- HBB gene
- AR inheritance
30
Which thalassemia is referred to as "major/minor"
beta
31
What is the genotype of an alpha-thalassemia silent carrier?
| Trait?
- a/aa
| - a/-a OR --/aa
32
What is the genotype for a beta-thalassemia trait?
-/B
33
Does an alpha-thal trait have a low MCV?
| Beta-thal trait?
yes, low for both
34
When in life are alpha- and beta- chaines made?
alpha: in utero
beta: after birth
35
Gamma chains
made through first year life to protect the infant
36
Which thalassemia genotype is more common in the Southeast Asian population? Black Americans?
- Asian: aa/--
| - Black: -a/-a
37
What does low MCV plus normal hemoglobin electrophoresis suggest?
alpha-thal trait
38
What does low MCV and increased HbA2 suggest?
beta-thal trait
