The case #2. Biochemistry.

I am going to share the biochemistry case with you guys today which leads me to understand the one of the mechanism of DNA damage what I have learned so far.

At the beginning of my post I am going to present the one of the USMLE style question from the book: First Aid Q&A for the USMLE step 1.Tao Le, Seth K. Bechis. Second Edition. 2009 p. 18.

A 6- year old boy presents to his pediatrician with skin lesions all over his body. For several years he has been very sensitive to sunlight. Neither the boy’s parents nor his siblings have the same skin lesions or sensitivity. Biopsies of several of the boy’s lesions reveal squamous cell carcinoma. Which mutation would one expect to see in this patient’s DNA?

A. Methylation of the gene

B. Missense mutation in the gene

C. Nonsense mutation in the middle of the gene

D. Point mutation within the enhancer region

E. Point mutation within the operator region

F. Point mutation within the promoter region

G. Thymidine dimers

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This is the rare disease which affects less than 200,000 people in the US population. Anyway I have had twice the question about this disorder.

In order to answer this question you have to know the types of DNA damage.

  1. Depurination. About 5 000 purines (A’s or G’s) per day are lost from DNA of each human cell when the N-glycosyl bond between the purine and deoxyribose sugar-phosphate is broken. This is the most frequent type of lesion and leaves the deoxyribose sugar-phosphate with missing purine base.
  2. Deamination of cytosine to uracil. About 100 cytosines (C)per day are spontaneously deaminated to uracil (U). If the U is not corrected back to a C, then on replication, instead of the occurrence of a correct C-G base pairing, a U-A base pairing will occur.
  3. Pyrimidine dimerization. Sunlight (UV radiation) can cause covalent linkage of adjacent pyrimidines, forming, for example, thymine dimers.High-yield Genetics. Ronald W. Dudek, John E. Wiley. 2009. p. 21.

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The official answer:

The correct answer is G. This patient has xeroderma pigmentosa (XP), an autosomal recessive disease characterized by a defect in excision repair. This disease results in an inability to repair thymidine dimers that can form in the presence of ultraviolet light. This can lead to the development of skin cancer and photosensitivity.

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You have to learn for the exam:

  1. XP is an autosomal recessive disorder in which the effected individuals are hypertensive to sunlight (ultraviolet radiation).
  2. XP is caused by inability to remove pyrimidine dimers due to a genetic defect in one or more of the nucleotide excision repair enzymes.
  3. Clinical features include: acute sun sensitivity with sunburnlike reaction, severe skin lesions aroun the eyes and eyelids, and malignant skin cancers (basal and squamous cell carcinomas and melanomas) whereby most individuals die by 30 years age. High-yield Genetics. Ronald W. Dudek, John E. Wiley. 2009. p. 70.

The image of the patient with XP

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