Biochemistry - Genetics Part 1 Flashcards
Approximately what percentage of individuals with von Hippel-Lindau disease will develop bilateral renal cell carcinomas?
50%
The vascular tumors of von Hippel-Lindau disease are commonly seen in which parts of the nervous system?
Retina, cerebellum, medulla
What is the pathophysiology of von Hippel-Lindau disease?
A tumor suppressor is deleted, leading to constitutive expression of hypoxia-inducible factors and an overabundance of vascular growth factors
The defect that leads to von Hippel-Lindau disease is found on chromosome _____.
3 (remember: Von Hippel-Lindau = 3words for chromosome 3)
What is the mode of inheritance of albinism?
Autosomal recessive
What is the mode of inheritance of 1antitrypsin deficiency?
Autosomal recessive
What is the mode of inheritance of phenylketonuria?
Autosomal recessive
What is the mode of inheritance of the thalassemias?
Autosomal Recessive
What is the mode of inheritance of sickle cell disease?
Autosomal recessive
What is the mode of inheritance of the glycogen storage diseases?
Autosomal recessive
What is the mode of inheritance of most mucopolysaccharidoses
Autosomal recessive
Most mucopolysaccharidoses are inherited in a(n) _____-_____ pattern, except for _____ _____.
Autosomal Recessive ;
Hunter’s Disease
Most sphingolipidoses are inherited in a(n) _____-_____ pattern, except for _____ _____.
Autosomal recessive ;
Fabry’s Disease
What is the mode of inheritance of hemochromatosis?
Autosomal recessive
What is the pattern of inheritance of cystic fibrosis?
Autosomal recessive
Cystic fibrosis results from a defect in which gene? Which chromosome? Which ion channel?
CFTR ; 7 ; chloride
Patients with cystic fibrosis characteristically have mucus plugs that disturb the function of which three organs?
The pancreas, the lungs, and the liver
Which two pathogens are the most likely to cause recurrent pulmonary infections in a patient with cystic fibrosis?
Pseudomonas species and Staphylococcus aureus
Recurrent pulmonary infections in patients with cystic fibrosis result in what pulmonary pathology?
Bronchiectasis
An infant with failure to thrive also had meconium ileus as a newborn. What is the most likely diagnosis?
Cystic Fibrosis
How is cystic fibrosis diagnosed?
High concentrations of chloride ions in the sweat
A male patient with cystic fibrosis asks you whether he will be able to have children; what is your response?
Unfortunately, males with cystic fibrosis are infertile due to bilateral absence of the vas deferens
A patient with cystic fibrosis is at increased risk for the deficiency of what four vitamins?
Vitamins A, D, E, and K, all of which are fat soluble
What is the most common lethal genetic disease among Caucasians?
Cystic Fibrosis
Treatment with what drug helps to loosen mucous plugs in patients with cystic fibrosis?
N-acetylcysteine
How does N-acetylcysteine free up mucous plugs?
It cleaves the disulfide bonds that connect mucous glycoproteins
What is the pattern of inheritance of fragile X syndrome?
X-linked recessive
remember: Be Wise, Fool;s GOLD Heeds False Hope
What is the pattern of inheritance of Duchenne’s muscular dystrophy?
X-linked recessive
remember: Be Wise, Fool;s GOLD Heeds False Hope
What is the pattern of inheritance of haemophilia A and B?
X-linked recessive
remember: Be Wise, Fool;s GOLD Heeds False Hope
What is the pattern of inheritance of Fabry’s Disease?
X-linked recessive
remember: Be Wise, Fool;s GOLD Heeds False Hope
What is the patten of inheritance of G6PD deficiency?
X-linked recessive
remember: Be Wise, Fool;s GOLD Heeds False Hope
What is the pattern of inheritance of Hunter’s Syndrome?
X-linked recessive
remember: Be Wise, Fool;s GOLD Heeds False Hope
What is the pattern of inheritance of ocular albinism?
X-linked recessive
remember: Be Wise, Fool;s GOLD Heeds False Hope
What is the pattern of inheritance of Lesch-Nyhan syndrome?
X-linked recessive
remember: Be Wise, Fool;s GOLD Heeds False Hope
What is the pattern of inheritance of Bruton’s agammaglobinaemia?
X-linked recessive
remember: Be Wise, Fool;s GOLD Heeds False Hope
What is the pattern of inheritance of Wiskott-Aldrich Syndrome?
X-linked recessive
remember: Be Wise, Fool;s GOLD Heeds False Hope
What conditions does the following pneumonic help you remember, and how are they all linked?
Be Wise, Fool’s GOLD Heeds False Hope
Bruton's agammaglobinaemia Wiskott-Aldrich Syndrome Fabry's Disease G6PD deficiency Ocular albinism Lesch-Nyhan Syndrome Duchenne Muscular Dystrophy Haemophilia A and B Fragile X Syndrome Hunter's Disease
They are all X-linked recessive conditions
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
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
Duchenne’s muscular dystrophy is caused by a deletion of what gene?
The dystrophin gene (remember: Duchenne;s = Deleted Dystrophin)
Is the loss of the dystrophin gene in Duchenne;s muscular dystrophy the result of frameshift, missense, nonsense, or silent mutations?
Frameshift mutation
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
At what age do Becker;s and Duchenne;s muscular dystrophy present?
Before the age of 5 years
In what muscle group does weakness normally begin in patients with Duchenne;s muscular dystrophy?
Pelvic girdle muscles
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 manoeuvre; the action is necessary due to the weakness of the proximal muscles
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 psuedohypertrophy due to fibrofatty replacement of the muscle and you would expect muscle weakness
What organ other than skeletal muscle is affected in Duchenne;s muscular dystrophy?
Heart
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
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
How is muscular dystrophy diagnosed?
Biopsy of skeletal muscle and elevated creatine phosphokinase
Fragile X syndrome is caused by a defect in which gene?
FMR1; the name of the gene stands for Familial Mental Retardation
What are the two most common genetic causes of mental retardation?
Down’s Syndrome and Fragile X Syndrome
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 = eXtra large testes, jaw and ears)
What triplet is expanded in fragile X syndrome and what is the result of this repeat?
CGG; aboormal methylation of the FMR1 gene
True or False? Fragile X syndrome is associated with chromosomal breakage.
True
Name four diseases that result from trinucleotide repeat expansion.
Huntington’s Disease, myotonic dystrophy, Friedrich’s ataxia, Fragile X Syndrome (remember: Try (tri nucleotide) hunting for my fried eggs X)
What does anticipation refer to in genetic disease?
Anticipation involves an increase in disease severity and an earlier age of onset in successive generations
Myotonic dystrophy is associated with a _____ (CTG/CGG) repeat, while fragile X syndrome has a _____ (CTG/CGG) repeat.
CTG; CGG
remember myoTonic dystrophy = CTG, fraGile X = CGG
Huntington;s disease has a _____ repeat, while Friedreich;s ataxia is a repeat of _____ nucleotides.
CAG; GAA
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’s Syndrome
A newborn is diagnosed with Down syndrome. She is vomiting bilious material. What is the most likely cause?
Duodenal atresia
A newborn is diagnosed with Down syndrome. He has a heart murmur on examination. What is the most likely cause?
Atrial Septal Defect
What type of atrial septal defect is most common in patients with Down syndrome?
Septum-primum type
What is the most common chromosomal disorder?
Down’s Syndrome
Patients with Down syndrome who are more than 35 years old have an increased risk of what neurodegenerative disease?
Alzheimer’s Disease
Patients with Down syndrome have an increased risk of what type of leukemia?
ALL
Ninety-five percent of cases of Down syndrome are caused by the _____ of homologous chromosomes during the cell division process of _____.
Nondisjunction; meiosis
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
What is the most common genetic mechanism leading to Down syndrome?
Meiotic nondisjunction
What results in the prenatal quad screen indicate possible Down syndrome?
Alpha fetoprotein, hCG, unconjugated oestriol, and inhibin A
Down syndrome is also known as trisomy _____.
21 (remember Drinking age = 21)
Which trisomy is the most common: 13, 18, or 21? What is the least common?
21 (1:700)
13 (1:15,000)
What is the other name for trisomy 18?
Edwards Syndrome (Election age = 18)
What are the clinical features of trisomy 18?
Mental retardation, rocker-bottom feet, micrognathia, low-set ears, clenched hands, prominent occiput, congenital heart disease
What is the prognosis for a patient with trisomy 18?
Death within the first year of life
A baby has low-set ears, micrognathia, a prominent occiput, rocker bottom feet, and clenched hands. What is the most likely diagnosis?
Edwards Syndrome
A newborn has microphthalmia, microcephaly, cleft lip, cleft palate, and polydactyly. What is the most likely diagnosis?
Patau’s Syndrome
Patau;s syndrome is also known as trisomy _____.
13 (Puberty = 13)
What are the clinical manifestations of trisomy 13?
Severe mental retardation, rocker-bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, congenital heart disease
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
The life expectancy for patients with trisomy 21 is _____ (1 year/20-40 years/45-50 years).
45-50 years
What is a Robertsonian translocation?
It is a nonreciprocal translocation of chromosome pairs, such that chromosomes carry genetic information in an uneven manner
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
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
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
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’s or Patau’s Syndrome
The two types of chromosomal inversions are called _______ and _____inversions.
Pericentric and paracentric
In chromosomal inversions, _____ (pericentric/paracentric) inversion involves the centromere and proceeds through meiosis.
Pericentric
In chromosomal inversions, _____ (pericentric/paracentric) inversion does not involve the centromere and does not proceed through meiosis.
Paracentric
How does a chromosomal inversion modify the affected chromosome?
It reverses one segment of the chromosome end-to-end
The deletion of the short arm of chromosome 5 leads to what disease?
Cri-du-chat syndrome
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
What are the clinical manifestations of cri-du-chat syndrome?
Microcephaly, moderate to severe ental retardation, high-pitched crying/mewing, epicanthal folds, cardiac abnormalities
Cri-du-chat syndrome is caused by a deletion of the _____ arm of chromosome ____.
Short ; 5
What disease is caused by a microdeletion of the long arm of chromosome 7?
Williams Syndrome
Among others, what connective tissue gene is deleted in Williams syndrome?
Elastin gene
Patients with Williams syndrome typically have _____ (coarse/masked/elfin) facies.
Elfin
A patient has an extreme friendliness towards strangers and cheerful disposition, with noted mental retardation and cardiovascular disease; what is the diagnosis?
Williams Syndrome
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
Microdeletions at chromosome 22q11 can present as a spectrum of diseases including which two recognized syndromes?
DiGeorge Syndrome or Velocardiofacial Syndrome
What disease is caused by microdeletions at 22q11 and involves defects of the thymus, the parathyroid, and the heart?
DiGeorge SYndrome
What disease is caused by microdeletions at 22q11 and involves defects of the palate, the face, and the heart?
Velocardiofacial syndrome
True or False? 22q11 Syndromes are associated with B cell deficiency.
False ; 22q11 syndromes are associated with T cell lymphocyte deficiency due to thymic aplasia
True or False? 22q11 Syndromes are associated with hypercalcemia.
False ; 22q11 syndromes are associated with hypocalcaemia due to parathyroid aplasia
Name 5 findings associated with 22q11 deletion syndromes.
CATCH-22 ; Cleft Palate, Abnormal facies, Thymic aplasia, Cardiac defects, Hypocalcaemia
What embryonic structures are altered in 22q11 syndromes?
These syndromes are due to aberrant development of the third and fourth branchial pouches
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
