Quiz 1 conditions Flashcards
1
Q
Mutation in sickle cell anemia occurs in this gene
A
Chromosome 11 beta-globin gene
2
Q
Type of point mutation that occurs in Sickle cell anemia
A
Missense (amino acid switch; Val –> Glu)
3
Q
Type of point mutation that occurs in thalassemia
A
Nonsense
4
Q
In thalassemia, there is a lack in production of this
A
Beta-globin
5
Q
2 mutations that can cause Beta-thalassemia
A
Nonsense point mutation
Abnormal splicing due to mutation in non-coding regions
6
Q
Some breast cancers have extra gene copies of this
A
Her2 gene (product is a growth factor receptor)
7
Q
Entire regions of these two chromosomes are transposed in chronic myeloid leukemia
A
9 and 22
8
Q
In chronic myeloid leukemia, this promoter becomes adjacent to ABL (tyrosine kinase) and acts as a perpetual on switch
A
BCR
9
Q
In chronic myeloid leukemia, BCR promoter becomes adjacent to this
Results in unregulated cell proliferation
A
ABL (a tyrosine kinase)
10
Q
Type of mutation that occurs in chronic myeloid leukemia
A
Translocation
(Entire regions of chromosome 9 and 22 are transposed)
11
Q
Disease caused by an expansion of CTG repeats at the 3’ untranslated region of DMPK gene, a protein kinase
Results in muscle generation with slowed relaxation phase
A
Myotonic dystrophy
12
Q
Myotonic dystrophy is broadly caused by this
A
Expansion of trinucleotide repeats
13
Q
In myotonic dystrophy, there is an expansion of CTG repeats in this gene
A
DMPK (protein kinase)
14
Q
Cilia-related protein that is responsible for sensing pressure and fluid flow, especially in the kidney
A
Polycystin
15
Q
Autosomal dominant polycystin disease involves a loss of function of polycystin due to mutation in this gene
A
PKD-1
16
Q
Adenomatous polyposis is caused by a mutation in the adenomatous polyposis coli (APC) gene, and exhibits this inheritance pattern
A
Autosomal dominant
(although both gene copies must be lost)
17
Q
Adenomatous polyposis coli (APC) is involved in cellular signaling and this pathway
A
WNT pathway (promotes cell proliferation –> cancer)
18
Q
a1-Antitrypsin (A1AT) deficiency exhibits this type of inheritance
A
Autosomal recessive
19
Q
A1AT protein turns off this activity
Deficiency results in inappropriate digestion of patient’s tissue proteins
A
WBC protease
20
Q
Glucose-6-phosphate dehydrogenase deficiency exhibits this inheritance
A
X-linked recessive
21
Q
X-linked recessive condition that results in inability to inactivate ROS, shortening RBCs lifespan
A
Glucose-6-phosphate dehydrogenase deficiency
22
Q
Type of lysosomal storage disease resulting from inability to degrade glycosaminoglycans
A
Mucopolysaccaridoses
23
Q
All mucopolysaccharidoses result in these 2 main symptoms
A
Coarse facial features and Skeletal dysplasia
24
Q
X-linked recessive deficiency of iduronate-2-sulfatase
A
Hunter syndrome
25
Mucopolysaccharidosis involving no corneal clouding and Death >10 years, some into adulthood
Hunter syndrome
26
autosomal recessive deficiency of alpha-1-iduronidase
Hurler syndrome
27
Hunter syndrome is due to a deficiency in this enzyme
Iduronate-2-sulfatase
28
Hurler syndrome is due to a deficiency in this enzyme
Alpha-1-iduronidase
29
Mucopolysaccharidosis involving Normal appearance at birth, Hepatosplenomegaly begins at 6-12 months, Corneal clouding, Heart valve insufficiency, Macroglossia, Skeletal dysplasia and coarseness
Death 6-10 years
Hurler syndrome
30
Which mucopolysaccharidosis involves corneal clouding and earlier death?
(More severe form)
Hurler syndrome
31
Autosomal recessive sphingolipidosis caused by a Glucocerebrosidase deficiency
Gaucher disease
32
Gaucher disease is due to a deficiency in this enzyme that is involved in degradation of cell membranes of RBCs and WBCs
Glucocerebrosidase
33
In Gaucher disease, this compound accumulates in macrophages and bone marrow
Glucocerebrosides
34
Levels of RBC, WBC, and platelets in Gaucher disease
All low (cytopenia)
35
Wrinkled tissue paper look from distended lysosomes is seen in this disease
Gaucher disease
36
Wrinkled tissue paper appearance to macrophages in Gaucher disease is caused by an accumulation of this in lysosomes
Glucocerebrosides
37
Sphingolipidosis that involves adult onset and 20x risk of Parkinson's disease
Splenomegaly, cytopenias, bone fracture risk
Gaucher disease
38
Autosomal recessive sphingolipidosis caused by a beta-hexosaminidase A deficiency
Tay-Sachs disease
39
Enzyme deficient in Tay Sachs disease
Beta-hexosaminidase A
40
Tay-Sachs disease results in an accumulation of this in all cells of the body
GM2 gangliosides
41
Most important symptom in Tay-Sachs disease
Neuronal accumulation of Gm2 gangliosides --> neurodegeneration
42
Sphingolipidosis where patients are normal appearance and physical exam at birth except for markedly increased startle reflex
Tay-Sachs disease
43
Tay-Sachs disease is most common in this ethnic population
East European Jewish
44
East European Jewish population have a high rate of these 2 diseases
Tay-Sachs disease and Niemann-Pick disease
45
In Tay-Sachs disease, GM2 gangliosides accumulate in the brain and result in these 2 main symptoms
Macrocephaly
Cherry-red macula
46
Which of the following sphingolipidoses involves a cherry-red macula?
Gaucher, Tay-Sachs, Niemann-Pick
Tay-Sachs > and Niemann-Pick Type A
47
Which of the following sphingolipidoses involves adult onset?
Gaucher, Tay-Sachs, Niemann-Pick
Gaucher disease
48
Sphingolipidosis that is an autosomal recessive deficiency of sphingomyelinase
Niemann-Pick disease
49
In Niemann-Pick disease, sphingomyelin accumulate in lysosomes of these 2 organs
Brain and liver
50
In Niemann-Pick disease, this accumulates in lysosomes of brain and liver
sphingomyelin
51
Whorled myelin bodies are characteristic of this sphingolipidosis
Tay-Sachs disease
52
Type of Niemann-Pick disease that involves severe mental deterioration; death by 3 years
CNS deterioration, hepatosplenomegaly, lymphadenopathy
Type A
53
Type of Niemann-Pick disease that involves Hepatosplenomegaly and minimal CNS involvement
Milder; survive to adulthood
Type B
54
Type of Niemann-Pick disease that involves alveolar thickening (leading to dyspnea (short of breath) and low pO2)
Type B
55
Lifespan of Hurler disease
6-10 years
56
Lifespan of Hunters disease
>10 years, some into adulthood
57
Lifespan of Gaucher disease
Near normal lifespan
58
Lifespan of Tay Sachs disease
3 years
59
Lifespan of Niemann-Pick Type A disease
3 years
60
Lifespan of Niemann-Pick Type B disease
Adulthood
61
Macrophage foam cell filled with sphingomyelin is seen in this disease
Niemann-Pick disease
62
Autosomal recessive deficiency of muscle phosphorylase
Involves exercise intolerance, fatigue, inability to mobilize glucose (no elevation of lactate with exercise), muscle cramps/pain with exercise (elevated CK due to muscle damage)
Muscle cell damage --> myoglobin release --> myoglobinuria
McArdle disease
63
Enzyme deficient in McArdle disease
Muscle glycogen phosphorylase
64
Autosomal recessive deficiency of hepatic glucose-6-phosphatase
Inability to mobilize glucose from liver to blood (hypoglycemia), Hepatomegaly
Von Gierke disease
65
Enzyme deficient in Von Gierke disease
Hepatic glucose-6-phosphatase
66
Autosomal recessive deficiency of alpha-glucosidase, a lysosomal enzyme (multisystem disorder)
Inability to cleave glycogen (glucose deficiency in heart)
Muscle weakness, cardiomyopathy (death in early childhood), vacuolar myopathy
Pompe disease
67
Enzyme deficient in Pompe disease
Alpha-glucosidase (lysosomal glycogen enzyme)
68
Condition caused by a point mutation resulting in replacement of a glycine residue with another amino acid in collagen molecule
Results in weak collagen, which is a major structural protein in all solid connective tissues
Frequent bone fractures, even in utero
Hearing loss due to defective ossicles
Translucent ocular sclera
Poor dentition
Osteogenesis imperfecta
69
Translucent ocular sclera is seen in this disorder of collagen
Osteogenesis imperfecta
70
First amino acid in the collagen side chain that when mutated prevents the formation of stable, compact collagen fibers
Is mutated to other amino acid in Osteogenesis imperfecta
Glycine
71
Autosomal dominant disorder caused by a defect in fibrillin protein
Involves dolichostenomelia (overgrowth of long bones), Pectus excavatum/carinatum, scoliosis, long face, prominent supraorbital ridges
Cardiovascular (mitral valve prolapse, aortic regurgitation, aortic aneurysm)
Marfans syndrome
72
Protein that is a scaffold for elastic fibers in ECM
Defective in Marfans syndrome
Fibrillin
73
Inheritance pattern of Marfans syndrome
Autosomal dominant
74
Abnormal fibrillin in Marfans syndrome results in decreased sequestration and increased levels of this which is involved in inflammation
TGF-beta
75
Symptom seen in Marfans syndrome where weak ciliary zonules lead to dislocation of lens
Ectopia lentis
76
Defective fibrillin protein in Marfans syndrome leads to defect in this type of tissue, causing cardiovascular problems
Connective tissue
77
Genetic disorder resulting in defective collagen
AR, AD, X-linked forms
Produced by many genes (genetic heterogeneity)
Very variable but common thread is fragile collagen
Susceptible to trauma, poor wound healing, susceptible to organ rupture, corneal rupture, hypermobile joints (dislocations), hyperextensible skin
Ehlers-Danlos syndrome
78
Autosomal dominant disorder with loss/reduced function of LDL cholesterol receptor
Homozygosity has additive effect (codominance)
Early cardiovascular diseases
Tendon xanthomas
Familial hypercholesterolemia
79
Ectopia lentis is seen in this disorder caused by a protein defect
Marfans syndrome
80
X-linked disorder (but does not show classic X-linked inheritance)
FMR gene on Xq27.3 has increased numbers of CGG trinucleotides, which elongate in maternal oocyte
Males: Dysmorphic ears, Long face with prominent jaw, Macroorchidism after puberty, Mental retardation
Females: May show mental impairment or learning disability and premature ovarian failure
Fragile X syndrome
81
Fragile X syndrome is caused by this
FMR gene on Xq27.3 has increased numbers of CGG trinucleotides
82
In Fragile X syndrome, trinucleotides on FMR gene Xq27.3 elongate in this
Maternal oocyte
83
Autosomal dominant condition caused by trinucleotide repeat mutation
Expansion occurs during spermatogenesis
Middle age neurodegenerative changes
Due to misfolded proteins which are neurotoxic
Hereditary but not congenital
Huntington disease
84
Trinucleotide repeat expansion in Huntington disease occurs during this
Spermatogenesis
85
Condition where maternal genes of region 15q12 are silenced by imprinting and paternal genes are lost by deletion
Prader-Willi syndrome
86
Condition where paternal genes of region 15q12 are silenced by imprinting and maternal genes are lost by deletion
Angelman syndrome
87
Are paternal or maternal genes lost by deletion in Prader-Willi syndrome?
Paternal
88
Are paternal or maternal genes lost by deletion in Angelman syndrome?
Maternal
89
Does this describe Prader-Willi or Angelman syndrome:
Intellectual disability, Short stature, Hyperphagia (eat a lot), Obesity, Small hands/feet, Hypogonadism
Prader-willi syndrome
90
Does this describe Prader-Willi or Angelman syndrome:
Intellectual disability, Microcephaly, Ataxia, Seizures, Inappropriate laughter
Angelman syndrome
91
Condition with Mitochondrial inheritance that involves progressive bilateral loss of central vision
Leber hereditary oculomotor neuropathy
92
Inheritance pattern of Leber hereditary oculomotor neuropathy
Mitochondrial inheritance
93
Condition with Characteristic craniofacial features: epicanthal folds, upward slanted palpebral fissures, flat face, flat occiput, speckled irises (Brushfield spots), mild microcephaly, flat nasal bridge, small sometimes misshapen ears
Congenital heart defects in 50%, GI defects, Musculoskeletal defects
Down syndrome
94
Trisomy 21 describes this condition
Down syndrome
95
Chromosomal abnormality in Down syndrome
Trisomy 21
96
Chromosomal abnormality in Patau syndrome
Trisomy 13
97
Trisomy 13 describes this condition
Patau syndrome
98
Condition described by:
Death by age 1 usually
Severe intellectual disability, Rocker bottom foot, Microphthalmia, Microcephaly, Cleft lip and palate, Polydactyly, Cutis aplasia, congenital heart disease, polycystic kidney disease, Omphalocele
Patau syndrome
99
Condition described by: Death by age 1 usually
Prominent occiput, Rocker bottom feet, Intellectual disability, Clenched fists, low set ears, Micrognathia, congenital heart disease, Omphalocele, Myelomeningocele
Edward syndrome
100
Chromosomal abnormality in Edward syndrome
Trisomy 18
101
Trisomy 18 refers to this condition
Edward syndrome
102
DiGeorge syndrome involves this chromosomal abnormality
22q11.2 deletion
103
CATCH-22: Cardiac, Abnormal face, Thymic hypoplasia, Cleft palate, Hypoparathyroid -22
Describes this chromosomal abnormality
22q11.2 deletion (e.g. DiGeorge syndrome)
104
Condition characterized by:
Thymic hypoplasia results in T-cell deficiency immune defects
Low lymphocyte counts → more viral infections
Hypoparathyroidism → low calcium → tetany (muscle rigidity)
Heart defects: tetralogy and persistent truncus arteriosus
DiGeorge syndrome (22q11.2 deletion)
105
Condition caused by Deletion of chromosome 5 short arm
Laryngeal problems (cat cry)
Hypotonia, hypertelorism, high arches palate, intellectual disability, microcephaly
Survive to adulthood but higher mortality in infancy
Cri du Chat syndrome
106
Chromosomal abnormality in Cri du Chat syndrome
Deletion of chromosome 5 short arm
107
Condition characterized by:
Laryngeal problems (cat cry)
Hypotonia, hypertelorism, high arches palate, intellectual disability, microcephaly
Survive to adulthood but higher mortality in infancy
Cri du Chat syndrome
108
Condition caused by Excess X chromosome material in a male
Invariably have hypogonadism - small testes, genitalia, cryptorchidism
Reduced testosterone results in high FSH and LH
Elevated estrogens may promote feminization phenotype
Pubic hair distribution, gynecomastia (also increased risk of breast cancer), body habitus
Tall stature (excess copies of SHOX gene), mild cognitive disability, developmental delay, speech difficulties, deficient gross motor skills, extragonadal germ cell tumor, autoimmune disease
Klinefelter syndrome
109
Chromosomal abnormality in Klinefelter syndrome
Excess X chromosome material in a male
110
Condition caused by X chromosome monosomy
Short stature, cardiovascular abnormalities, lymph obstruction of neck (webbing or cystic hygroma), ovarian dysgenesis, reduced breast development, broad chest with wide spaced nipples, normal intelligence
Noted at birth: Lymphedema and webbed neck
Somatic abnormalities related to Xp: Fewer copies of SHOX gene (short stature homeobox gene), which regulates linear growth → short stature
Gonadal abnormalities related to Xq
Turner syndrome
111
Chromosomal abnormality in Turner syndrome
X chromosome monosomy
112
Condition where main features noted at birth include lymphedema and webbed neck
Turner syndrome
