Ataxia Telangiectasia

Cancers associated with heterozygous ATM mutations (8)

(1) Breast (2) Ovarian (3) Prostate (4) Pancreatic (5) Stomach (6) Bladder (7) ALL (8) Lymphoma

Non-cancer symptoms of A-T (5)

(1) Cerebellar ataxia (2) Oculocutaneous telangiectasias (3) Oculomotor apraxia (4) Choreoathetosis (5) Immunodeficiency

Cytogenic location of ATM gene

11q22.3

Median age of death in A-T

20-30s

At what age should a person with a pathogenic heterozygous ATM variant start mammograms/MRI to screen for breast cancer?

40 years old

The Val2424Gly (c.7271T>G) missense mutation incurs what lifetime risk of breast cancer?

50-69%

Causative gene of Ataxia Telangiectasia

ATM

What does ATM mean?

Ataxia Telangiectasia Mutated

Inheritance pattern of Ataxia Telangiectasia

Autosomal Recessive

When should a person with a pathogenic heterozygous ATM variant get a bilateral prophylactic mastectomy (BPM)

Based on family history and the patients wishes

Surveillance for ovarian cancer in individuals with pathogenic heterozygous ATM variants

Consider with family history

TRUE or FALSE: ATM mutations that confer susceptibility to breast cancer are the same as those that occur in Ataxia-Telangiectasia

False

Which missense mutation in ATM is shown to segregate with disease in multiple families, and has been suggested to confer a higher risk for breast cancer than other published ATM variants (up to a 50-69% LTR)

Val2424Gly (c.7271T>G)

TRUE or FALSE: A-T patients are sensitive to radiation

True

Surveillance for breast cancer in individuals with pathogenic heterozygous ATM variants

Mammogram/MRI starting at 40 years old (unless family history of cancer at a younger age)

ATM variants associated with breast cancer tend to be what type of variants?

Missense

Function of the ATM gene

Protein kinase that recognizes damaged/broken DNA strands and coordinates DNA repair by activating enzymes that fix the broken strands; Plays a role in the development of the nervous and immune systems