chromosomal breakage syndrome

Keerthana . Cbms12267

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.

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.

Major types of syndromes

Louis bar syndrome.

Fanconi anemia.

Bloom syndrome.

Xeroderma pigmentosum.

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.

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.

Cerebellar ataxia

Ocular ataxia

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.

How does it cause• It caused by a genetic mutation

• A mutated gene called ATM produces a mutated ATM protein.

Normal ATM gene

• A Serine-Protein KinaseEx. p53, BRCA1

• Senses Double Stranded Breaks in DNA.

• Activates cell cycle checkpoints.

Abnormal ATM gene

• It inhibits DNA repair.

• It produce Missense mutations.

• It leads multiple mutations thus causing cancer.

Fanconi anemia

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.

Clinical Manifestations• Fanconi Anemia can be characterized by

physical abnormalities, such asabnormalities of the thumbs, forearms, skeletal system, eyes, kidneys and urinary tract, ear, heart, gastrointestinal system, oral cavity, and central nervous system; hearing loss ; hypopigmentation.

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

Function of FA genes• DNA repair

• Cell cycle control

• Oxygen sensitivity

• Apoptosis and telomere maintenance

• Haemopoiesis

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.

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.

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

Bloom syndrome

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.

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.

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.

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.

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

Xeroderma pigmentosum

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.

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

cause

Xeroderma Pigmentosum

Treatment

• There is no cure for XP so far.

• Many management methods to cope with the problems

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