Gene expression disorders/Questions and case studies

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Questions[edit | edit source]

  1. Translation of mRNA with a size of 2200 bp resulted in a product of size:
    • A – 1100 bp
    • B – 494 amino acid residues
    • C - 196 kDa
    • D – 985 amino acid residues
  2. Tissue-specific mRNA editing is mainly provided by:
    • A – mitochondrial specific tRNAs
    • B – eRNA
    • C – gRNA
    • D – ribosomal RNA (rRNA)
  3. Moving the reading frame cannot normally result in this change:
    • A – to create a new cap – placing the cap in a new place
    • B – to extend the protein
    • C – to change the biological half-life of the protein
    • D – to create a new stop codon
  4. Which answer is incorrect? Nuclear gene expression is regulated by:
    • A – using Tf
    • B – in the promoter region
    • C – using nuclear receptors
    • D – by feedback according to the amount of mRNA in the mitochondria
Question 1.
  • A – Wrong. A polypeptide is produced during translation.
  • B – Correct. One amino acid is encoded by a triplet. Part of the mRNA is made up of regions that are not subject to translation (5'UTS on average 100 bp, 3'UTS on average 600 bp).
  • C – Wrong. One amino acid contributes approximately 100 Da. It is unlikely that, for example, carbohydrates would contribute to the molecular weight of 75%.
  • D – Wrong. The maximum number of amino acids in a polypeptide is theoretically 2200:3 = 733.

Question 2.

  • A – Wrong. Mitochondrial tRNAs do not affect editing.
  • B – Wrong. There are no eRNAs.
  • C – Correct. Specific gRNAs are involved in editing by recognition, anchor and polyU sequences.
  • D – Wrong. Ribosomal RNAs have a different function in proteosynthesis.

Question 3.

  • A – Correct. Frameshifting occurs downstream of the cap signal site, usually in the first exon first.
  • B – Wrong.
  • C – Wrong.
  • D – Wrong.

Question 4.

  • A – Wrong. Transcription factors are commonly involved in the regulation of gene expression.
  • B – Wrong. On the contrary, this region is typical for the regulation of gene expression.
  • C – Wrong. Gene expression is sometimes regulated, for example, by means of nuclear hormone receptors.
  • D – Right. The amount of mitochondrial mRNA has no effect on the regulation of nuclear gene expression.

Case reports[edit | edit source]

Newborn with focal convulsions[edit | edit source]

The patient, aged 4 days, was left in the neonatal unit because of the occurrence of focal convulsions. Biochemical examination was repeatedly normal. Epileptic activity was detected during the EEG. The pediatric neurologist evaluated the findings as benign focal neonatal epilepsy. An extensive family history revealed a frequent occurrence of epilepsy in the family. A 283insGT mutation in KCNQ2 was demonstrated in the patient.


  1. Which biochemical examination is meant?
  2. What is the biochemical basis of hereditary epilepsy?
  3. What does the abbreviation 283insGT mean and what does such a mutation lead to?
  1. S-Ca, S-K, S-Na, P-glucose, S-Mg, P-lactate, S-bilirubin, blood gases, blood pH, urine for ketone bodies.
  2. “Depolarization war” between potassium and sodium channels, caused by e.g. mutations in genes for the alpha subunit of potassium channels, e.g. KCNQ2 (20q13.3), KCNQ1, KCNQ3, HERG (Ikr), KCNA1.
  3. Insertion of two pairs of nucleotides into triplet (codon) 283, which leads to a shift of the reading frame (formation of a polypeptide with a nonsense sequence of amino acids from the site of mutation and the formation of an early or late stop codon).

Patient with hypotension and in metabolic disorder[edit | edit source]

A 4-year-old patient was admitted to the pediatric ward because he had lost consciousness. The examination revealed hypotension, S-K 2.6 mmol/l, pH 7.8 and HCO3 52. The Nordin index was 1.4. A P124L mutation was detected in CLC-Kb.


  1. What disease could it be? And what would be the other laboratory findings to confirm the diagnosis?
  2. What is the Nordin index?
  3. What is the cause of this syndrome?
  4. What is CLC-Kb and what does the abbreviation P124L stand for?
  1. Bartter syndrome. Repeated hypokalemic alkalosis, increased salt loss in urine, hyperreninemia and hyperaldosteronism, hypercalciuria, hyperprostaglandinuria, normomagnesemia.
  2. U-calcium/U-creatinine ratio (mmol/mmol).
  3. Mutations in the genes for proteins for the transport of chlorides or potassium in the outer or inner membrane of the cells of the renal tubules (e.g. in the thick part of the ascending limb of the loop of Henle): CLC-Kb, ROMK (ATP sensitive inwardly rectifying K+ channel), NKCC2 (bumetanide-sensitive Na -K-2Cl cotransporter).
  4. The CLC-Kb chloride channel belongs to a family of about 10 CLC (voltage-gated chloride channels). Other types of chloride channels include ELG (extracellular ligand-gated) and CFTR. The abbreviation P124L means the substitution of proline for leucine at the 124th position of the polypeptide chain.

Patient with colorectal cancer[edit | edit source]

The patient, age 52, was examined on an outpatient basis for fatigue, low fever, gastrointestinal problems and repeated findings of admixture of fresh blood and sometimes mucus in the stool. During rectoscopy, a biopsy was performed from the suspected tumor site. The biopsy sample was examined histologically (adenocarcinoma) and molecularly genetically for the presence of mutations in the K-ras gene (substitution in position 2 of codon 12, GGT→GCT).


  1. Which other laboratory tests would be suitable for monitoring the patient?
  2. What is the K-ras gene and what is its significance?
  3. What is the consequence of the given point mutation?
  1. E.g. CEA, FW (erythrocyte sedimentation rate), acute phase proteins.
  2. Point mutations in the K-ras gene are associated with a multistage process of colorectal cancer development. Gene expression of K-ras leads to the synthesis of the p21ras protein, which is an essential part of cellular signaling cascades. It is functionally related to cytoplasmic receptors. Point mutations in exon 1 (codons 12 and 13) and exon 2 (codon 61) of the K-ras gene inhibit the GTPase activity of the p21ras protein and thereby contribute to uncontrolled proliferation and malignant transformation of intestinal cells.
  3. This is a point substitution that results in the exchange of one amino acid for another, in this case Gly12Ala. This amino acid substitution leads to a decrease in the GTPase activity of the RAS protein (resulting in a slow inactivation of the GTP-RAS signal that leads to an excessive cellular response to the receptor signal).

Patient with liver cirrhosis[edit | edit source]

A 55-year-old female patient visited her family physician for persistent weakness, lethargy, loss of libido, and joint pain. Six months ago, she was diagnosed with diabetes mellitus. Physical examination revealed hepatomegaly and hyperpigmentation of the skin. The EKG showed signs of cardiomyopathy. Biochemical tests and a liver biopsy were performed. DNA was isolated from peripheral leukocytes and examined for the presence of the C282Y mutation in the HLA-H (HFE) gene.


  1. What biochemical tests would be appropriate to investigate? What histological examination was performed on the biopsy specimen?
  2. What is the disease and how is it treated?
  3. What is the cause of this disease?
  4. What does the abbreviation C282Y mean?
  1. Serum: AST 1.1 uct/l, ALT 0.9 uct/l, Fe 60 umol/l, ferritin 630 ug/l, transferrin 2.57 g/l. Staining of the preparation for the presence of iron.
  2. Hereditary hemochromatosis. It is treated with controlled venipuncture and Desferal.
  3. Excessive deposition of Fe ions in tissues. The cause is mutations in the HFE gene formerly known as HLA-H. The protein product of this gene shows homology to HLA class I proteins, including binding to β2-microglobulin. Under physiological conditions, the HFE protein occupies receptors for transferrin on the cell surface and thereby regulates the transition of the complex of iron ions and transferrin into the cell. The HFE gene C282Y mutation in a homozygous arrangement was found in 85% of cases of hereditary hemochromatosis. The second protein, the erroneous overproduction of which is apparently associated with manifestations of hemochromatosis, is the product of the SFT (stimulator of Fe transport) gene.
  4. Replacement of cysteine ​​for tyrosine at the 282nd codon of the respective polypeptide.

Links[edit | edit source]

Related articles[edit | edit source]

Source[edit | edit source]

  • MASOPUST, Jaroslav – PRŮŠA, Richard. Patobiochemie metabolických drah. 1. edition. Praha : Univerzita Karlova, 1999. 182 pp. pp. 214–218. ISBN 80-238-4589-6.