Genetics Flashcards
What is the difference between a somatic mutation and a germline mutation?
Somatic mutation affects one cell in non-germline tissues and are non-heritable
Germline mutation affects cell in egg or sperm and is passed onto every cell in offspring, causing family cancer syndromes
What is an example of oncogenic cancer.
Oncogene ABL fuses sporadically with BCR, making BCR-ABL fusion protein and causes leukaemia
What is HNPCC?
Hereditary non-polyposis colorectal cancer
Mutation in mismatch repair genes
Adenoma-carcinoma sequence for polyp formation
AKA Lynch syndrome
Where do HNPCC tumours usually present?
Proximal colon
Often endometrial cancers for women
What are some options for breast surveillance?
Breast awareness
Annual or clinical exam
Mammography
MR screening for highest risk
What are the main genes tested for in breast cancer?
BRCA1 BRCA2 PALB2 PTEN P53 CHEK2
What are the main genes tested for in ovarian cancer?
BRCA1 BRCA2 Lynch genes RAD51C RAD51D
What is a management option for BRCA1/2 carriers?
Prophylactic mastectomy
Significantly reduces risk
What are some drawbacks of prophylactic oophererctomy for primary ovarian cancer?
Peritoneal carcinomatosis may still occur
Induces surgical menopause
What are some options for surveillance of CRC?
Colonoscopy (Frequency depends on risk)
Prophylactic aspirin
What are some risks of genetic testing for familial cancers?
Does not detect all mutations
Continued risk of sporadic cancer
Efficacy of interventions variable
May result in psychosocial or economic harm
What are the 3 ways multi-system disorders can be inherited?
Chromosomal (Trisomy 21)
Single gene disorders (myotonic dystrophy, CF, Duchenne’s)
Multifactorial (diabetes)
Why do some mutations give multi-system disorders?
Single genes may have diverse functions
Single gene widely expressed in different tissues
Gene may be tissue specific but tissue is in many different systems
How does neurofibromatosis type 1 (NF1) present?
Cafe au lait spots Neurofibromas Axillary freckling Lisch nodes Optic glioma Thinning of long bone cortex Raised BP
Which gene causes NF1?
17q
What are the main features of NF2?
Acoustic neuroma
CNS and spinal tumour
CAL spots
NF2 gene is on chromosome 22
What is the classic triad of Tuberous Sclerosis (TS)?
Epilepsy
Learning difficulty
Skin lesions
Myoclonic seizures
Which genes cause TS?
TSC1
TSC2
How are relatives at risk of TS screened?
Skin signs Retinal exam Cranial MR scan Renal USS Echocardiogram
How does myotonic dystrophy present?
Bilateral late-onset cataract Muscle weakness Stiffness Myotonia Low motivation Bowel problems Heart block
Why may an adult be referred for pre-symptomatic testing?
Diagnosis Predictive testing Carrier testing Family history Fetal loss or recurrent miscarriage
Is risk estimation more difficult for single gene or multifactorial conditions?
Single gene
Especially those with high penetrance
What is a requirement of testing for children and adolescents?
Must be some potential medical benefits
What is mean age onset for MND?
55
What are some clinical features of MND?
Progressive muscle weakness, wasting and increased reflexes
Pure motors signs with fasciculations
Cognition spared
Death due to respiratory failure
What is another name for MND?
Amyotrophic lateral sclerosis
What happens in MND?
Superoxide Dismutase
Catalysis of conversion of intracellular superoxide radicals
Is Huntington’s disease usually youth or adult onset?
Adult
How does HD affect movement?
Chorea
Athetosis
Myoclonus
Rigidity
How does HD affect cognitive changes?
Poor planning and memory Subcortical dementia (executive function)
How does HD affect personality?
Irritable Apathetic Loss of empathy Disinhibition Self centred
How does HD affect psychiatry?
Depression
Paranoia
Psychosis
What are some disadvantages of a positive predictive test?
Less hope
Still uncertain with onset
Risk to offspring
Potential insurance/mortgage problems
What are some advantages of a positive predictive test?
Uncertainty removed
Make plans for future
Arrange surveillance
Inform children or decide whether or not to have them
What are some requirements for predictive testing?
Info must be useable for prevention or treatment
Require proper counselling
Children only tested if potential medical benefits
Third parties should have no access
Susceptibility testing requires adequate information about uncertainty
What are some common features of down’s syndrome?
Flattened face Almond shaped slanted eyes Short neck Small ears, hands and feet White spots in iris Tongue sticks out Single palmar crease Curved pinkies towards thumb Poor muscle tone Short Small malleolus
What are the main characteristics of Kallman syndrome?
Delayed or absent puberty
Impaired sense of smell
