All of the following about hereditary breast and ovarian cancer are true except?
Autosomal recessive inheritance
BRCA 1 and BRCA 2 normally maintain genomic integrity by acting as a tumor suppressor gene and regulating DNA repair, transcription transactivation and the cell cycle
2 hit hypothesis- Somatic LOF by the second allele occurs by loss of heteozygosity, intragenic mutation or promoter hypermethylation
Founder effect seen in Ashkenazi Jews
Germ line mutation of BRCA2 is associated with male breast cancers (6-14%)
Familial hypercholesterolemia is characterized by all of the following except?
Autosomal Dominant inheritance
Mutation of LDL receptor found in 59% of French Canadian with familial hypercholesterolemia
LDL-R binds apoB100 and apoE
decreased LDL cholesterol
Management is mainly low fat high carbohydrate diet with 3 classes of drugs: bile sequestrants (Cholestyramine resin), HMG CoA reductase inhibitors and nicotinic acid
All of the following about G6PD deficiency are true except
X-linked recessive inheritance
G6PD is the first enzyme in HMP shunt critical for generating NADPH which is required to regenerate glutathione
Rare symptomatic females - due to skewing of X chromosome inactivation
G6PD B- is less severe than G6PD A-
A 25 year old African-American man is given anti-malarial prophylaxis for a trip to West Africa. Over the next week he develops increasing fatigue. On Physical exam there are no abnormal findings. Lab studies show a hematocrit of 30% and peripheral blood smear shows red blood cells with numerous Heinz bodies. There is a family history of this disorder, with males but not females, affected. What is the most likely diagnosis
Sickle cell disease
Pyruvate dehydrogenase deficiency type 1
None of the above
A 30 year old woman has felt a mass in her right breast for 6 months. On physical exam there is a 5 cm mass in the right breast and it is firm, non tender with lymphadenopathy. A fine needle aspiration is performed and cytologic exam shows carcinoma cells. Right mastectomy with axillary lymph node dissection is performed and microscopic exam shows a poorly differentiated carcinoma that is negative for estrogen and progesterone receptors and negative for HER2/neu. One axillary node shows micrometastases. Her 32 year old sister is found to have a similar lesion. Which is the following is the most likely risk factor for this woman's breast cancer?
BRCA 1 mutation
loss of p53
Both of the above
none of the above
All of the following about Hereditary hemochromatosis are correct except
Autosomal recessive with reduced penetrance
90-95% of patients are homozygous for a Cys282Tyr mutaion
Mutant HFE interferes with hepcidin signaling resulting in stimulation of enterocytes and macrophages to release iron
Hepcidin is synthesized in liver and released to block further iron absorption when iron supplies are adequate
Males are protected against this condition
46 year old man who has had worsening arthritis and swelling of his feet for the past year. On exam he has rales audible in all lung fields. A CXR showed cardiomegaly and pulmonary edema. Lab studies showed Hgb of 13, Hct of 39.1% MCV 86fl, platelet count of 255,000/ul and WBC count 5920/ul. His serum iron is 406 microgram/ml, with iron binding capacity of 440 micrograms/ml and ferritin 830 ng/ml. What is the most likely diagnosis
All of the following about Hemophilia are true except?
Both Hemophilia A and B are X-linked recessive
Factor 9 - Most common mutation is an inversion deleting the carboxyl terminus of factor 9
Factor 9 - severe hemophilia during childhood that spontaneously resolves at puberty as factor 9 levels nearly normalize
Therapy is replacement of the factor that is deficient
All of the following regarding HPNCC are true except
Mutation in MLH1, MSH2) DNA mismatch repair gene mutation
Microsatellite instability occurs in 15-20% of HNPCC tumors
Microsatellite instability induced frame shift mutations in the transforming growth factor receptor II gene (TGFBetaR2)
All of the following are true regarding NIDDM except?
TCF7L2 significantly associated with NIDDM in Icelandic population and Pro12Ala mutation in PPARG in Finnish and Mexican Americans
More prone to develop ketoacidosis
HbA1c > 6.5% is more important that the actual glucose levels
A 57 year old man is found comatose. On exam he has decreased skin turgor. Lab studies show a blood glucose of 780 mg/dl. Urinalysis reveals no ketosis or proteinuria, but there is 4+ glucosuria. What is the most likely diagnosis?
Combination of both because of hyperglycemia
24 hour old male baby is comatose and on lab studies shows Hyper ammonia, hypo citrullemia and urine showed orotic aciduria. Most likely diagnosis
CPS I deficiency
CPS II deficiency
All of the following are true about Retinoblastoma except?
Autosomal Dominant - LOF mutation on chromosome 13
Isodisomy is the most common type of mutation
Nearly half the mutations occurs at CpG dinucleotides (C --> T transition)
Unilateral disease in hereditary
All of the following for Tay-Sachs disease are true except?
Hexosaminidase A is a lysosomal enzyme made of HEXA + HEXB genes, Hexosaminidase A in the presence of activator protein, removes the N-terminal GalNAc from the ganglioside
Infantile - onset is characterized by neurological deterioration at 3-6 months of age and Juvenile onset usually manifests between 2-4 yrs of age and also characterized by neurological deterioration
Have normal levels of hexosaminidase B