Term
| How many genes are tehre in the human genome? |
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Definition
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Term
| The average person carries how many mutated genes? |
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Definition
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Term
| Is spinal muscular atrophy a congenital or adult onset disease? |
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Definition
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Term
| What is incomplete penetrance? |
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Definition
| when the mutated gene can be present without the characteristic phenotype |
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Term
| What types of genetic disorders often show incomplete penetrence? |
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Definition
| autosomal dominant conditions |
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Term
| What is the % chance a gene will manifest as a phenotype? |
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Definition
|
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Term
| What is the incidence of hereditary hemochromatosis? |
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Definition
|
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Term
| What is the incidence of AD polycystic kidney disease? |
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Definition
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Term
| What is the MC lethal single gene disorder? |
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Definition
|
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Term
| WHat is the MC lethal autosomal recessive disorder in caucasians? |
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Definition
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Term
| What is the incidence of cystic fibrosis? |
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Definition
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Term
| Erhlers Danlos syndrome is due to a defect in... |
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Definition
|
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Term
| What are teh phenotypic characteristics of erhlers danlos syndrome? |
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Definition
| stretchy skin, hyperextensible joints, splenic artery aneurysm/rupture |
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Term
| Why is genetic testing so much more complex than normal labs? |
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Definition
| psychological aspects, require genetic counseling, privacy, genetic discrimination |
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Term
| Name a good resource for physicians about genetic testing? |
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Definition
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Term
| What types of information is used to diagnose single gene disorders? |
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Definition
| clinical, biochemical, and molecular testing |
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Term
| What are the different types of molecular tests performed? |
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Definition
| panel testing, targeted testing or whole gene sequencing |
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Term
| What is the gene mutation in tuberous sclerosis? |
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Definition
|
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Term
| Name the gene that is mutated in cystic fibrosis? |
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Definition
|
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Term
| Name the gene that is mutated in hereditary hemochromatosis? |
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Definition
|
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Term
| Whati s the gene that is mutated in hereditary hemochromatosis? |
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Definition
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Term
| What is the gene that is mutated in hypertrophic cardiomyopathy? |
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Definition
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Term
| What gene is mutated in ADPKD? |
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Definition
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Term
| What gene is mutated in pancreatitis? |
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Definition
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Term
| What gene is mutated in FAP? |
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Definition
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Term
| What single gene disorder might present as syncope? What should you ask about in the history? |
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Definition
| hypertrophic cardiomyopathy; sudden death |
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Term
| What single gene disorder might present as weight loss/mental status change? |
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Definition
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Term
| What cancers should you ask about in teh family history of patients whom you suspect to have BRCA1/2? |
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Definition
| breast, ovarian, prostate, colon |
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Term
| Describe how the sweat chloride test is performed? |
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Definition
| 75mg sweat collected over 30 minutes; positive if Cl- > 60 mEq/L on two occasions |
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Term
| Sweat chloride test provides an accurate diagnosis in what percent of cases? |
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Definition
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Term
|
Definition
|
|
Term
| How many different CFTR mutations are there? |
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Definition
|
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Term
| How many caucasians carry a CFTR mutation? |
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Definition
|
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Term
| What testing method is used for the first round of CF molecular tests? |
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Definition
| mutational panel testing that tests for the first 23 more common mutations |
|
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Term
| What is the most common CFTR mutation and how common is it? |
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Definition
| MC mutation= delta F508 in 66% of caucasian carriers |
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Term
| What percent of caucasians, blacks and askenazi jews affected with CF will have a normal initial molecular test? |
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Definition
| 85% of caucasians, 75% of blacks, 95% of ashkenazi jews |
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Term
| Once a patients CF mutation is determined, other familes can be tested by... |
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Definition
| targeted mutational analysis |
|
|
Term
| What is the chance of a caucasian couple having a child with CF? |
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Definition
|
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Term
| If you are caucasian, have a sister with CF and want to have kids with another caucasian, you're chances of having a child with CF is... |
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Definition
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Term
| When you suspecta a patient might have factor V leiden thrombophilia, you should ask about family history of... |
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Definition
| spontaneous abortion, PE, DVT, stroke, etc. |
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Term
| What is the biochemical test for factor V leiden? |
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Definition
| APC resistance assay; compare patient's PTT both with and without activated protein C because APC is an anticoagulant that binds with FV to inactivate it |
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Term
| What is a normal APC resistance assay? |
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Definition
| APC inactivates FV and PTT is 2-3 times longer with APC |
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Term
| How good is the aPC resistance assay in determining if the patient has factor V leiden? |
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Definition
| 30% of patients with (+) APC resistance testing do not have F5L disease |
|
|
Term
| When is testing for the F5 mutation indicated? |
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Definition
| when APCR assayis positive |
|
|
Term
|
Definition
|
|
Term
| Describe the primary mutation of F5? |
|
Definition
|
|
Term
| How many americans carry one mutation for F5? |
|
Definition
|
|
Term
| How many americans carry 2 mutated F5 alleles? |
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Definition
|
|
Term
| What is the testing method used for F5 mutation? |
|
Definition
| single targeted mutation analysis because nearly all affected individuals have the same mutation |
|
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Term
| What kind of molecular testing method is used for sickle cell anemia? |
|
Definition
| single targeted mutation analysis |
|
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Term
| 100% of factor V leiden patients will have the G --> A single point mutation (with an aa change) at nucleotide _____ in the F5 gene detectable by targeted mutational testing. |
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Definition
|
|
Term
| What is the inheritance pattern of factor 5 leiden? |
|
Definition
| incomplete autosomal dominance |
|
|
Term
| What are the clinical consequences of having one mutated allele for factor V leiden? |
|
Definition
| 3% risk/year for venous thrombosis and SAB; no increased mortality rate |
|
|
Term
| What is the clinical consequence of having two mutated alleles for factor V leiden? |
|
Definition
| 12% risk/year for venous thrombosis and SAB with increased mortality rate |
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Term
| If one parent has factor V leiden mutation, what next test is indicated to determine status of the children/potential children? |
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Definition
| targeted mutational analysis of the spouse |
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Term
| By 20 yoa, a person with FAP will have what clinical manifestation of the disease? |
|
Definition
| 100s of precancerous polyps |
|
|
Term
| What is the penetrance factor of FAP? |
|
Definition
|
|
Term
| What is the lifetime colon cancer risk of a patient with FAP? |
|
Definition
|
|
Term
| What is the average age of onset of colon cancer in a patient with FAP? |
|
Definition
|
|
Term
| T/F HNPCC presents as colon cancer without preexisting polyps. |
|
Definition
| true (hereditary NONpolyposis colon cancer) |
|
|
Term
| What is the penetrance factor of HNPCC? |
|
Definition
|
|
Term
| What is the average age of onset for colon cancer in FAP? |
|
Definition
|
|
Term
| Besides colon cancer, people with FAP are also at risk for... |
|
Definition
| 10%= small bowel, 2% pancreas, 2% liver, 1% thyroid, <1% CNS |
|
|
Term
| Besides colon cancer, people with HNPCC are also at risk for... |
|
Definition
| 40% endometrium, 15% stomach, 10% ovary, 5% liver, 5% urinary tract, 2% small bowel, 2% CNS |
|
|
Term
| How do you differentiate clinical between FAP and HNPCC? |
|
Definition
| FAP has more than 100 colorectal adenomatous polyps; HNPCC has less than 100 |
|
|
Term
| Where is the APC locus for FAP? |
|
Definition
|
|
Term
| How many different mutations for APC are there? |
|
Definition
|
|
Term
| What is the prevalence of APC mutations? |
|
Definition
|
|
Term
| What is the testing method for APC? |
|
Definition
|
|
Term
| What percent of people affect with FAP have a negative initial molecular test? |
|
Definition
|
|
Term
| Whole gene sequences for FAP works in ___% of affected people. |
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Definition
|
|
Term
| What is the next step for working up FAP if whole gene sequencing is negative? |
|
Definition
| DNA testing that is able to detect large, or whole gene deletions rather than single aa shifts |
|
|
Term
| What is the clinical part of diagnosing HNPCC? |
|
Definition
| based on HNPCC type of CA < 50 yoa and positive family history |
|
|
Term
| What is genetic heterogeneity? |
|
Definition
| when more than 1 major genes can cause disease |
|
|
Term
|
Definition
| 3 major genes (mismatch repair genes i.e. MMR) are disease causing |
|
|
Term
| Where are the loci of the genes that cause HNCPC? |
|
Definition
| MLH1 locus= 3p21; MSH2 locus= 2p22; MSH6= 2p16 |
|
|
Term
| How many different mutations are there at the MLH1 locus for HNPCC? |
|
Definition
|
|
Term
| How many different mutations are there for the MSH2 locus? |
|
Definition
|
|
Term
| How many different mutations are there for HNPCC at the MSH 6 locus? |
|
Definition
|
|
Term
| T/F All genes for HNPCC are autosomal dominant. |
|
Definition
|
|
Term
| How much does it cost to test for HNPCC and what are the testing methods? |
|
Definition
| >4,000; mutation scanning, whole gene sequencing, deletion analysis |
|
|
Term
| What percent of patients with HNPCC mutations have mutations at the different loci? |
|
Definition
| 60% at MLH1; 30% at MSH2; >5% MSH6; <5% other |
|
|
Term
| What percent of people with HNPCC testing will HNPCC will ultimately have negative molecular testing? |
|
Definition
|
|
Term
| What is the best method for detecting mutations in HNPCC? |
|
Definition
|
|
Term
| In what types of carriers is HNPCC less penetrant? |
|
Definition
| females (40-50% of women develop cancer versus 70-80% of men develop cancer) |
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