Genetics Flashcards
What is nonsense mediated decay?
Getting rid of proteins produced that don’t conform to normal standards (either stop being too early or too late)
What is polygenic risk?
Multiple genes contributing towards familiar risk
What is leucocornea?
White eye in retinoblastoma
What happens in hereditary non-polyposis colon cancer? (HNPCC/lynch syndrome)
Mutation in mistmatch repair genes
Excess of cancers in adenoma carincoma sequence
Early CRC
Effects proximal colon
What is a germline mutation?
Where mutation is present in egg/sperm and are henceforth heredtary
Cause cancer family syndromes
What is an oncogne?
A gene that controls cell processes that, if it mutates, will be enough to start the cancer process
What are the lifetime cancer risks of the BRCA genes?
Breast - 60-80% (early onset)
Secondary primary breast cancer - 40-60%
Ovarian 20-50%
Increased risk of prostate + breast cancer in men
When do you suspect hereditary cancer syndrome?
Cancer in 2+ relatives Early age of diagnosis Multiple primary tumours Bilateral or multiple rare cancers Charactersitc pattern of tumours Evidence of autosomal dominant transmission
What are the options for breast cancer surveillance?
Early clinical surveillance 5yrs before 1st cancer in family
Annual clinical breast exams
Mammography Every 2 yrs from 35-40, yearly from 40-50
Every 18 months if high risk from 50
What is the benefit of a prophylatic oophrectomy?
Eliminates risk of primary ovarian cancer (peritoneal cancers can still occur)
Risk of subsequent BRCA halved
How is colorectal cancer surveyed in lynch syndrmoe?
Colonoscopy every 2 years from 25 if high risk
If moderate risk once at 35 and once at 55
How is endometrial cancer screened for in lynch syndrome?
Transvaginal ultrasound
No recommendations
What are the limitations of genetic testing?
doesn’t detect all mutations
Continued risk of sporadic cancer
Efficacy of interventions variable
May result in psychosocial/economic harm
What cancers are associated with Li-Fraumeni syndrome?
Soft-tissue sarcoma Osteosarcoma Breast cancer Brain/CNS tumours Adrencortical carcinoma Acute luekemia
What are the modes of inheritance for multi-system disorders?
Any possible eg - Chromosomal Single gene Poly gene
What are some important multi-system disorders?
NF1 Myotonic dystrophy Tuberous clerosis CF Downs
How do disorders cause mlti-system involvement?
As several (or just one) gene with diverse functions are involved This can be widely expressed in different tissues >However expression in tissues can be different
What are the mechanisms of adult onset genetic disease?
Single gene
Chromosomal
Mitochondrial
Multifactorial
What are some common problems in multi-system disease?
Variable expression within + between families
Present to a large number of specialists
FH easily missed
What gene pattern is neurofibromatosis type 1 (NF1)?
Autosomal dominant
17q tumour supressor gene affected
What is the diagnostic criteria for NF1 (neurofibromatosis type 1)?
2+ of: café au lait spots - 6 or more neurofibromas - 2 or more axillary freckling Lisch nodules (specks in iris) optic glioma thinning of long bone cortex family history
What other features can accompany NF1?
Macrocephaly Short sature Dysmorphic features Learning difficulties Epilepsy Scoliosis Raised BP Neoplasia
How do you manage NF1?
Annual review of affected individuals + at risk children until diagnosis excluded Check for: BP Spine for scoliosis Tibia for unusua angulation Visual acuity/fields Educational assesment
What are the main features of NF2?
Acoustic neuromas (often bilateral)
CNS + spinal tumours
A few CAL spots
