Biochem - Genetics (Part 1) Flashcards
1
Q
Approximately what percentage of individuals with von Hippel-Lindau disease will develop bilateral renal cell carcinomas?
A
50%
2
Q
The vascular tumors of von Hippel-Lindau disease are commonly seen in which parts of the nervous system?
A
Retina, cerebellum, medulla
3
Q
What is the pathophysiology of von Hippel-Lindau disease?
A
A tumor suppressor is deleted, leading to constitutive expression of hypoxia-inducible factors and an overabundance of vascular growth factors
4
Q
The defect that leads to von Hippel-Lindau disease is found on chromosome _____.
A
3 (remember: Von Hippel-Lindau = 3 words for chromosome 3)
5
Q
What is the mode of inheritance of albinism?
A
Autosomal recessive
6
Q
What is the mode of inheritance of 1 antitrypsin deficiency?
A
Autosomal recessive
7
Q
What is the mode of inheritance of phenylketonuria?
A
Autosomal recessive
8
Q
What is the mode of inheritance of the thalassemias?
A
Autosomal recessive
9
Q
What is the mode of inheritance of sickle cell disease?
A
Autosomal recessive
10
Q
What is the mode of inheritance of the glycogen storage diseases?
A
Autosomal recessive
11
Q
What is the mode of inheritance of most mucopolysaccharidoses?
A
Autosomal recessive
12
Q
Most mucopolysaccharidoses are inherited in a(n) _____-_____ pattern, except for _____ _____.
A
Autosomal-recessive; Hunter’s disease
13
Q
Most sphingolipidoses are inherited in a(n) _____-_____ pattern, except for _____ _____.
A
Autosomal-recessive, Fabry’s disease
14
Q
What is the mode of inheritance of hemochromatosis?
A
Autosomal recessive
15
Q
What is the pattern of inheritance of cystic fibrosis?
A
Autosomal recessive
16
Q
Cystic fibrosis results from a defect in which gene? Which chromosome? Which ion channel?
A
CFTR; 7; chloride
17
Q
Patients with cystic fibrosis characteristically have mucus plugs that disturb the function of which three organs?
A
The pancreas, the lungs, and the liver
18
Q
Which two pathogens are the most likely to cause recurrent pulmonary infections in a patient with cystic fibrosis?
A
Pseudomonas species and Staphylococcus aureus
19
Q
Recurrent pulmonary infections in patients with cystic fibrosis result in what pulmonary pathology?
A
Bronchiectasis
20
Q
An infant with failure to thrive also had meconium ileus as a newborn. What is the most likely diagnosis?
A
Cystic fibrosis
21
Q
How is cystic fibrosis diagnosed?
A
High concentrations of chloride ions in the sweat
22
Q
A male patient with cystic fibrosis asks you whether he will be able to have children; what is your response?
A
Unfortunately, males with cystic fibrosis are infertile due to bilateral absence of the vas deferens
23
Q
A patient with cystic fibrosis is at increased risk for the deficiency of what four vitamins?
A
Vitamins A, D, E, and K, all of which are fat soluble
24
Q
What is the most common lethal genetic disease among Caucasians?
A
Cystic fibrosis
25
Treatment with what drug helps to loosen mucous plugs in patients with cystic fibrosis?
N-acetylcysteine
26
How does N-acetylcysteine free up mucous plugs?
It cleaves the disulfide bonds that connect mucous glycoproteins
27
What is the pattern of inheritance of fragile X syndrome?
X-linked dominant (remember: **B**e **W**ise, **F**ool's **GOLD H**eeds **F**alse **H**ope; **F**ragile X)
28
What is the pattern of inheritance of Duchenne's muscular dystrophy?
X-linked recessive (remember: **B**e **W**ise, **F**ool's **GOLD H**eeds **F**alse **H**ope; **D**uchene)
29
What is the pattern of inheritance of hemophilia A and B?
X-linked recessive (remember: **B**e **W**ise, **F**ool's **GOLD H**eeds **F**alse **H**ope; **H**emophilia A)
30
What is the pattern of inheritance of Fabry's disease?
X-linked recessive (remember: **B**e **W**ise, **F**ool's **GOLD H**eeds **F**alse **H**ope; **F**abry's)
31
What is the pattern of inheritance of glucose-6-phosphate dehydrogenase deficiency?
X-linked recessive (remember: **B**e **W**ise, **F**ool's **GOLD H**eeds **F**alse **H**ope; **G**lucose-6-phosphate dehydrogenase)
32
What is the pattern of inheritance of Hunter's syndrome?
X-linked recessive (remember: **B**e **W**ise, **F**ool's **GOLD H**eeds **F**alse **H**ope; **H**unter's)
33
What is the pattern of inheritance of ocular albinism?
X-linked recessive (remember: **B**e **W**ise, **F**ool's **GOLD H**eeds **F**alse **H**ope; **O**cular albinism)
34
What is the pattern of inheritance of Lesch-Nyhan syndrome?
X-linked recessive (remember: **B**e **W**ise, **F**ool's **GOLD H**eeds **F**alse **H**ope; **L**esch-Nyhan)
35
What is the pattern of inheritance of Bruton's agammaglobulinemia?
X-linked recessive (remember: **B**e **W**ise, **F**ool's **GOLD H**eeds **F**alse **H**ope; **B**ruton's agammaglobulinemia)
36
What is the pattern of inheritance of Wiskott-Aldrich syndrome?
X-linked recessive (remember: **B**e **W**ise, **F**ool's **GOLD H**eeds **F**alse **H**ope; **W**iskott-Aldrich)
37
True or False? Hunter's syndrome has the same pattern of inheritance as Hurler's syndrome.
False; Hunter's syndrome has X-linked recessive inheritance, whereas Hurler's syndrome has autosomal-recessive inheritance
38
Why are female carriers of X-linked recessive disorders rarely affected?
There is random inactivation of X chromosomes in each cell, a process known as lyonization
39
Duchenne's muscular dystrophy is caused by a deletion of what gene?
The dystrophin gene (remember: Duchenne's = **D**eleted **D**ystrophin)
40
Is the loss of the dystrophin gene in Duchenne's muscular dystrophy the result of frameshift, missense, nonsense, or silent mutations?
Frameshift mutation
41
What is the pathophysiology of Duchenne's muscular dystrophy?
Dystrophin anchors muscle fibers in the membrane and lack of the protein leads to accelerated muscle breakdown
42
At what age do Becker's and Duchenne's muscular dystrophy present?
Before the age of 5 years
43
In what muscle group does weakness normally begin in patients with Duchenne's muscular dystrophy?
The pelvic girdle muscles
44
A 4-year-old boy needs to use his upper extremities to push against his legs in order to stand up. What is the name of this maneuver?
Gower's maneuver; the action is necessary due to the weakness of the proximal muscles
45
A 4-year-old boy with Duchenne's muscular dystrophy has hypertrophied calf muscles; what is the expected strength in his legs?
This is actually pseudohypertrophy due to fibrofatty replacement of the muscle and you would expect muscle weakness
46
What organ other than skeletal muscle is affected in Duchenne's muscular dystrophy?
Heart
47
What aspect of the dystrophin gene makes it particularly susceptible to mutation?
The dystrophin gene (*DMD*) is the largest known human gene, which allows a high rate of spontaneous mutations
48
Is Becker's muscular dystrophy more or less severe than Duchenne's muscular dystrophy?
Becker's muscular dystrophy is less severe and presents later in life
49
How is muscular dystrophy diagnosed?
Biopsy of skeletal muscle and elevated creatine phosphokinase
50
Fragile X syndrome is caused by a defect in which gene?
*FMR1* ; the name of the gene stands for Familial Mental Retardation
51
What are the two most common genetic causes of mental retardation?
Down syndrome and fragile X syndrome
52
A male patient has a long face, a large jaw, large ears, autism, and macroorchidism. What is the most likely diagnosis?
Fragile X syndrome (remember: Fragile **X** = e**X**tra large testes, jaw, ears)
53
What triplet is expanded in fragile X syndrome and what is the result of this repeat?
CGG; abnormal methylation of the *FMR1* gene
54
True or False? Fragile X syndrome is associated with chromosomal breakage.
TRUE
55
Name four diseases that result from trinucleotide repeat expansion.
Huntington's disease, myotonic dystrophy, Friedreich's ataxia, Fragile X syndrome (remember: **Try** (**tri**nucleotide) **hunting** for **my fried** eggs [**X**])
56
What does anticipation refer to in genetic disease?
Anticipation involves an increase in disease severity and an earlier age of onset in successive generations
57
Myotonic dystrophy is associated with a _____ (CTG/CGG) repeat, while fragile X syndrome has a _____ (CTG/CGG) repeat.
CTG; CGG (remember: myo**T**onic dystrophy = C**T**G, fra**G**ile X = C**G**G)
58
Huntington's disease has a _____ repeat, while Friedreich's ataxia is a repeat of _____ nucleotides.
CAG; GAA
59
A patient has a flat facial profile, prominent epicanthal folds, and a simian crease. This patient also has mental retardation. What is the most likely diagnosis?
Down syndrome
60
A newborn is diagnosed with Down syndrome. She is vomiting bilious material. What is the most likely cause?
Duodenal atresia
61
A newborn is diagnosed with Down syndrome. He has a heart murmur on examination. What is the most likely cause?
Atrial septal defect
62
What type of atrial septal defect is most common in patients with Down syndrome?
Septum-primum type
63
What is the most common chromosomal disorder?
Down syndrome
64
Patients with Down syndrome who are more than 35 years old have an increased risk of what neurodegenerative disease?
Alzheimer's disease
65
Patients with Down syndrome have an increased risk of what type of leukemia?
Acute lymphocytic leukemia
66
Ninety-five percent of cases of Down syndrome are caused by the _____ of homologous chromosomes during the cell division process of \_\_\_\_\_.
Nondisjunction; meiosis
67
What is the likelihood of a 20-year-old woman having a baby with Down syndrome? A 45-year-old woman?
1:1500; 1:25
68
What is the most common genetic mechanism leading to Down syndrome?
Meiotic nondisjunction
69
What results in the prenatal quad screen indicate possible Down syndrome?
-fetoprotein-human chorionic gonadotropin, estriol, and inhibin A
70
Down syndrome is also known as trisomy \_\_\_\_\_.
21 (remember: **D**rinking age = 21)
71
Which trisomy is the most common: 13, 18, or 21? What is the least common?
21 (1:700); 13 (1:15,000)
72
What is the other name for trisomy 18?
Edwards; syndrome (remember: Election age = 18)
73
What are the clinical features of trisomy 18?
Mental retardation, rocker-bottom feet, micrognathia, low-set ears, clenched hands, prominent occiput, congenital heart disease
74
What is the prognosis for a patient with trisomy 18?
Death within the first year of life
75
A baby has low-set ears, micrognathia, a prominent occiput, rocker bottom feet, and clenched hands. What is the most likely diagnosis?
Edwards' syndrome (trisomy 18)
76
A newborn has microphthalmia, microcephaly, cleft lip, cleft palate, and polydactyly. What is the most likely diagnosis?
Patau's syndrome (trisomy 13)
77
Patau's syndrome is also known as trisomy \_\_\_\_\_.
13 (remember: **P**uberty = 13)
78
What are the clinical manifestations of trisomy 13?
Severe mental retardation, rocker-bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, congenital heart disease
79
True or False? Newborns with trisomy 13 and newborns with trisomy 18 have similar expected life spans.
True; infants with both of these conditions are expected to die before the age of 1 year
80
The life expectancy for patients with trisomy 21 is _____ (1 year/20-40 years/45-50 years).
45-50 years
81
What is a Robertsonian translocation?
It is a nonreciprocal translocation of chromosome pairs, such that chromosomes carry genetic information in an uneven manner
82
What makes chromosomes 13, 14, 15, 21, and 22 candidates for Robertsonian translocations?
They are acrosomal chromosomes, which means that the centromere is located near one end rather than in the middle
83
How do acrosomal chromosomes align to create a Robertsonian translocation?
The long arms match up and fuse at the centromere, losing the short arms of the chromosomes
84
Does a Robertsonian translocation always result in a loss of genetic material?
A balanced translocation retains all genetic material and will not have any abnormal phenotype; if the translocation is unbalanced, genetic material is lost and abnormalities result
85
True or False? An unbalanced Robertsonian translocation may cause a chromosomal imbalance, but rarely miscarriage or stillbirth.
False; unbalanced translocations may result in miscarriage, stillbirth, or chromosomal imbalance such as Down or Patau's syndrome
86
The two types of chromosomal inversions are called _______ and \_\_\_\_\_inversions.
Pericentric and paracentric
87
In chromosomal inversions, _____ (pericentric/paracentric) inversion involves the centromere and proceeds through meiosis.
Pericentric
88
In chromosomal inversions, _____ (pericentric/paracentric) inversion does not involve the centromere and does not proceed through meiosis.
Paracentric
89
How does a chromosomal inversion modify the affected chromosome?
It reverses one segment of the chromosome end-to-end
90
The deletion of the short arm of chromosome 5 leads to what disease?
Cri-du-chat syndrome
91
A newborn has microcephaly and epicanthal folds and produces a high-pitched crying or mewing sound. What is the most likely diagnosis?
Cri-du-chat syndrome
92
What are the clinical manifestations of cri-du-chat syndrome?
Microcephaly, moderate to severe mental retardation, high-pitched crying/mewing, epicanthal folds, cardiac abnormalities
93
Cri-du-chat syndrome is caused by a deletion of the _____ arm of chromosome \_\_\_\_.
Short; 5
94
What disease is caused by a microdeletion of the long arm of chromosome 7?
Williams syndrome
95
Among others, what connective tissue gene is deleted in Williams syndrome?
The elastin gene
96
Patients with Williams syndrome typically have _____ (coarse/masked/elfin) facies.
Elfin
97
A patient has an extreme friendliness towards strangers and cheerful disposition, with noted mental retardation and cardiovascular disease; what is the diagnosis?
Williams syndrome
98
In spite of their mental retardation, in which cognitive area are patients with Williams syndrome typically advanced?
Patients with Williams syndrome typically have well-developed verbal skills
99
Microdeletions at chromosome 22q11 can present as a spectrum of diseases including which two recognized syndromes?
DiGeorge syndrome or velocardiofacial syndrome
100
What disease is caused by microdeletions at 22q11 and involves defects of the thymus, the parathyroid, and the heart?
DiGeorge syndrome
101
What disease is caused by microdeletions at 22q11 and involves defects of the palate, the face, and the heart?
Velocardiofacial syndrome
102
True or False? 22q11 Syndromes are associated with B cell deficiency.
False; 22q11 syndromes are associated with T lymphocyte deficiency due to thymic aplasia
103
True or False? 22q11 Syndromes are associated with hypercalcemia.
False; 22q11 syndromes are associated with hypocalcemia due to parathyroid aplasia
104
Name 5 findings associated with 22q11 deletion syndromes.
**C**left palate, **A**bnormal facies, **T**hymic aplasia, **C**ardiac defects, **H**ypocalcemia (remember: **CATCH-22**)
105
What embryonic structures are altered in 22q11 syndromes?
These syndromes are due to aberrant development of the third and fourth branchial pouches
106
True or False? 22q11 Syndromes are X-linked recessive and show anticipation.
False; 22q11 syndromes are due to microdeletions on chromosome 22 and have variable presentations
