1. chromosomal breakage
syndrome
Keerthana . C
bms12267

2. introduction
• A group of symptoms that collectively indicate or
characterize a disease, psychological disorder, or other
abnormal condition - Is known as syndrome.
• Syndrome causes serious or even fatal conditions.
• Syndromes may curable or incurable.
• Chromosomal breakage syndromes are conditions that occur
due to improper DNA repair.

3. How does CBS syndrome
cause?
 loss of DNA repair.
 Inter stand cross links.
 Genomic instability.
 Increase exchange between sister chromatids.
 Change in nucleotide.
 Double strand DNA breaks.

4. Major types of syndromes
 Louis bar syndrome.
 Fanconi anemia.
 Bloom syndrome.
 Xeroderma pigmentosum.

5. Louis bar syndrome
• This syndrome was first described in 1941 by French
physician Denise Louis-Bar.
• It is caused because of chromosomal instability.
• It is an autosomal recessive disease.
• It is a neuron degenerative disease mainly affects
cerebellum.

6. Types of louis bar
syndrome
 Cerebellar ataxia :- In-coordination, lack of balance in
body. It generally affect cerebellum.
 Ocular ataxia :- widening of small blood vessels in
conjuctiva.

7. Cerebellar ataxia

8. Ocular ataxia

10. ATM gene
• The ATM gene is located on chromosome 11.
• This protein is found in the cell nucleus.
• Acting with other proteins, their role is to activate the
cells to repair damaged DNA.

11. How does it cause
• It caused by a genetic mutation
• A mutated gene called ATM produces a mutated ATM
protein.

12. Normal ATM gene
• A Serine-Protein Kinase
Ex. p53, BRCA1
• Senses Double Stranded Breaks in DNA.
• Activates cell cycle checkpoints.

13. Abnormal ATM gene
• It inhibits DNA repair.
• It produce Missense mutations.
• It leads multiple mutations thus causing cancer.

18. Fanconi anemia

19. What is fanconi anemia?
• Fanconi anemia is one of the inherited anemias that
causes bone marrow failure.
• It is a condition that affects many parts of the body.
• 90 percent of people with Fanconi anemia have impaired
bone marrow function that leads to a decrease in the
production of all blood cells.
• It is autosomal recessive disorder.

20. Clinical Manifestations
• Fanconi Anemia can be characterized by physical
abnormalities, such as
abnormalities of the thumbs, forearms, skeletal system,
eyes, kidneys and urinary tract, ear, heart,
gastrointestinal system, oral cavity, and central nervous
system; hearing loss ; hypopigmentation.

21. FA genes
• We all have FA genes.
• It is located in chromosome 16.
• It is a protein coding gene.

23. Function of FA genes
• DNA repair
• Cell cycle control
• Oxygen sensitivity
• Apoptosis and telomere maintenance
• Haemopoiesis

24. FA pathway
• Proteins produced from these genes are involved in a cell
process known as the FA pathway.
• The FA pathway is activated when the process of
making new copies of DNA, called DNA replication
• The replication is blocked due to DNA damage.
• The FA pathway sends certain proteins to the area of
damage, which trigger DNA repair.

25. Continued...
• The FA pathway is particularly responsive to a certain
type of DNA damage known as interstrand cross-links
(ICLs).
• FA proteins produce FA core complex .
• The FA core complex activates two proteins, called
FANCD2 and FANCI
• these two proteins brings DNA repair proteins to the
area of the ICL.

27. Mutation in FA gene
Mutations in FA
disrupt FA pathway.
DNA damage is not repaired.
abnormal cell death or uncontrolled cell growth
CANCER

28. Bloom syndrome

29. What is bloom syndrome
• It is a inherited disorder.
• causes sun-sensitive skin changes, an increased risk of
cancer, and other health problems.
• It caused by mutation in BLM gene.
• Life span- 24 yrs.

30. symptoms
 dilated blood vessels
 reddening in the skin
 high-pitched voice
 Increased risk of diabetes,
 chronic obstructive pulmonary disease (COPD).
 infections of the upper respiratory tract, ears, eyes.

31. BLM gene
• The BLM gene is located on the long (q) arm of
chromosome 15 at position 26.1.
• they are known as the "caretakers of the genome.“
• They maintain structure and integrity of DNA.

32. Function of BLM gene
• The BLM gene provides instructions for making a
member of a protein family called helicases.
• Helicases are enzymes that bind to DNA and
temporarily unwind the two spiral strands (double
helix) of the DNA molecule.

33. Mutation in BLM gene
Mutated BLM gene
Mutated BLM protein
Frequency of sister chromatids exchange increased
Causes chromosome instability with gaps and breaks in
Genetic material
Uncontrolled cell growth
CANCER

34. Xeroderma pigmentosum

35. What is it?
• It Caused by an abnormality in an individual’s genome.
• It Can also be caused by environmental factors.
• It is a autosomal recessive disorder.
• When both parents are carrier, there is a 25% chance
that the child will be affected.

36. symptoms
• Skin - aging of skin, lips, eyes, mouth and
tongue, dark spots and dryness of skin.
• Eyes – photophobia, Bloodshot,
Cloudiness of the cornea,
Darkening of the skin of the eyelids
• Neurological disorder -Hearing loss,
Microcephaly, Poor coordination

37. cause

39. Xeroderma Pigmentosum
Treatment
• There is no cure for XP so far.
• Many management methods to cope with the problems

40. Thank u