Genetic Disease

Front 1

1. What is a Mendial disorder?
2. What does Marfan's syndrome present as?
3. What is the root of Marfan syndrome?

Back 1

1. A disorder arising from single gene defects
2. Very tall, long arms, and legs and a kyphotic spine often heart problems focused on chordae tendineae
3. Mutation in fibrillin-1 (sometimes TGF-beta is involved)

Front 2

1. What is the root of Ehlers Danlos syndrome?
2. What is the common theme in manifestation?
3. What is the only ehlers that does not have hyperextensibility of teh skin?

Back 2

1. Mutation in collagen
2. Skin that is too fragile or stretchy
3. Type IV- vascular

Front 3

1. What is a disease in the category "defects in receptor proteins"
2. How does it arise?

Back 3

1. Familial hypercholesterolemia
2. From mutation in the low density lipoprotein receptor or LDLR. LDLR is crucial for transporting LDL and IDL out of the blood, if it does not work get hypercholesterolemia
3x high - heterozygote 8x high- homozygote

Front 4

1. What are the 5 stages of LDLR life?
2. What molecule targets proteins in the golgi apparatus to lysosomes?
3. What does Tay Sachs disease not break down?
4. Presentation of tay sachs?

Back 4

1. Synthesis, transport, binding, clustering, recycling
2. Mannose 6-phosphate
3. GM2 ganglioside - leads to accumulated membrane lipids in lysosome (gangliosides) bc a deficiency of hexosaminidase A
4. Cherry red spot on the macula, poor muscle tone, and autosomal recessive inheritance. prevalent among jews

Front 5

1. In Neimann-Pick disease, what fails to form leading to an accumulation of what?
2. What organ enlargement is most prominent?
3. What is more deadly A or B?

Back 5

1. Fails to form sphingomyelinase leading to an accumulation of sphingomyelin
2. Spleen (filters blood)
3. A is, it involves CNS

Front 6

1. What gene is mutated in Neimann-Pick disease type C?
2. What does the normal protein do?
3. Clinical presentation?

Back 6

1. NPC1 or NPC2
2. Transports cholesterol from lysosomes to the cytoplasm. Accumulates cholesterol and gangliosides (same accumulant as in Tay-Sachs)
3. Heterogeneous, has progressive neurologic damage, marked by ataxia, vertical gaze palsy, dystonia, dysarthria, and psychomotor regression

Front 7

1. What is the defective protein in Gaucher disease?
2. Leads to an accumulation of what?
3. What does a gaucher cell look like (macrophage who accumulated 2)
4. Symptoms:

Back 7

1. Glucocerebrosidase
2. Glucocerebroside
3. crumpled tissue paper, should show diffuse iron staining
4. hepatosplenomegaly, anemia, leukopenia

Front 8

1. What is the accumulant in Hunter & Hurler syndrome?
2. Deficiency of what enzyme causes Hurler syndrome?
3. Hunter?

Back 8

1. Mucopolysaccharide (aka glycosaminoglycans) typically are found in the ECM
2. Alpha-L-iduronidase
3. Iduronate-2-sulfatase

Front 9

1. What are 2 main symptoms of Hurler syndrome (gargoylism)?
2. How is Hurler distinguished from Hunter?

Back 9

1. Valvular heart disease & corneal clouding
2. Hunter does not have corneal clouding, is X linked and milder

Front 10

1. In hepatic type glycogenoses, what is the enzyme deficiency (von Gierke disease)?
2. What does the deficiency lead to?

Back 10

1. Glucose 6-phosphatase
2. failure to release glucose from glycogen stores in the liver. leads to hepatomegaly and renomegaly

Front 11

1. In myopathic type glycogenoses, what is the enzyme deficiency? (McArdle syndrome)
2. What does the deficiency lead to?

Back 11

1. Muscle phosphorylase
2. Failure to use glycogen in glycolysis and do not produce expected amounts of lactic acid during exercise (develop severe cramping)

Front 12

1. In Pompe diseease, what is the enzyme deficiency?
2. What does it present with?

Back 12

1. Lysosomal glucosidase (acid maltase)
2. Massive cardiomegaly but also hepatosplenomegaly, death is typical within 2 yrs

Front 13

1. What is the gene defect in alkaptonuria (aka ochronosis)?
2. What does it cause?
3. What accumulates in the body?
4. What does it do to urine color?
5. What are the most serious consequences due to?

Back 13

1. Homogentisic oxidase
2. a blue-black discoloration in the ears, nose and cheeks which leads to severe damage of cartilage
3. Homogentisic acid
4. gives it a black color upon oxidation
5. Deposit of the pigment in joints leading to damage

Front 14

1. What are top characteristics of Down syndrome?

Back 14

1. Abundant neck skin, increase in beta-amyloid plaques, simian crease, congenital heart defects, predisposition to leukemia - trisomy 21

Front 15

1. Top characteristics for Klinefelter syndrome?

Back 15

1. Taller on average than average, (XXY), usually sterile, sub average intelligence -- must have at least 2 X to be klinefelters

Front 16

What is:
1. Genetic sex
2. Gonadal sex
3. Ductal sex
4. Phenotypic sex (genital sex)

Back 16

1. Presence or absence of Y chromosome
2. Histologic characteristics of gonads
3. presence of derivative of Wolffian (male) or mullerian (female) ducts
4. Appearance of external genitalia

Front 17

1. What is true hermaphroditism?
2. What is female pseudoherma.
3. Most common cause of 2?

Back 17

1. Presence of ovarian and testicular tissue (based on gonadal sex) through mosaicism
--Female or male refers to gonadal sex
2. Has ovaries with male external genitalia (genetically XX)
3. Congenital adrenal hyperplasia (autosomal recessive)

Front 18

1. What is male pseudohermaphroditism?
2. Caused by?

Back 18

1. Has testicular tissue but female genitalia. Y chromosome is present
2. Defect in androgen receptor (X-linked)

Front 19

1. What are the top 2 most common causes of mental retardation?
2. What is the repeat unit in fragile X syndrome?
3. Does expansion of the trinucleotide repeat occur during spermatogenesis or oogenesis?
4. What does this imply for the disease manifestation?
5. What is another symptom for it other then retardation

Back 19

1. Downs then Fragile-X
2. CGG
3. Oogenesis
4. Gets worse with each generation (man cannot pass it to his sons)
5. Macro-orchidism (large testicles)

Front 20

1.How are mitochondrial disorders inherited?
2. What do most involve?
3. E.g. of 1 what does lebers hereditary optic neuropathy lead to? (LHON)

Back 20

1. From the mother
2. Neuromuscular system
3. Bilateral loss of central vision leading to blindness

Front 21

1. What are 2 diseases that illustrate the genetic mechanism of imprinting?

Back 21

1. Prader-Willi and Angelman sindrome

Front 22

1. Where is the deletion in prader-Willi syndrome?
2. Where is the deletion in angelman syndrome?

Back 22

1. Paternal chromosome deletion (Paternal Prader-Willi is not active and the maternal is silenced by imprinting)
2. Maternal chromosome deletion (Maternal Angelman region is not active and the fathers is imprinted)

Front 23

Prader Willi vs Angelman
1. In which is truncal obesity and small hands symptoms?
2. In which is "happy puppet syndrome" a symptom?

Back 23

1. Prader willi
2. Angelman

Front 24

1. What enzyme is deficient in Tay-Sachs disease?
2. Leads to what?

Back 24

1. Hexosaminidase A
2. neurologic impairment, poor motor development and blindness

Front 25

1. What is the most likely factor in an otherwise asymptomatic infant with no family history of disorders who has a cleft lip?

Back 25

1. Multi factorial inheritance

Front 26

1. What are common symptoms of Edwards syndrome?
2. Common disease of galactosemia?
3. Aortic dissection?
4. Acute myocardial infarction?

Back 26

1. trisomy 18. low set ears, micrognathia, overlapping fingers, heart defects, rocker bottom feet
2. Hepatic schlerosis
3. Marfan syndrome
4. familial hypercholesterolemia

Front 27

1. Where do leiomyoma's occur most frequently?
2. Etiology of neurofibroma?
3. Would having multiple children in a generation suffer from a spontaneous new mutation be unlikely?

Back 27

1. in the uterus
2. multiple nodules on the dermis of varying size
3. Yes

Front 28

1. What is female pseudohermaphroditism?
2. What is a hygroma, horseshoe kidney, and aortic coarctation suggestive of?

Back 28

1. Have female internal structures (ovaries, uterus etc) but has ambiguous or male external genitalia... female refers to the genetic type
2. 45X Turners syndrome

Front 29

1. What is the inheritance pattern of type 1 Diabetes?
2. When doing a PCR for fragile X, what could a negative result mean?
2. After PCR, what is the next logical step?

Back 29

1. Multifactorial
2. either fetus is not affected, or there is a full mutation that is too large to be detected
3. Southern blot analysis of DNA

Front 30

1. What is a Robertsonian translocation?

Back 30

1. break occurs close to the centromeres of 2 chromosomes. Segments are transferred leading to a very large chromosome and a very small chromosome. Usu. the small is lost but ok b/c typically very redundant genes and is compatible with normal phenotype... can produce Downs

Front 31

1. What is a single Y sufficient to do?
2. What is a premutation?
3. What is heteroplasmy?

Back 31

1. Determine male sex
2. intermediate sized expansion of a trinucleotide repeat region that is insufficient to cause the disease
3. the presence of a mixture of more than one type of an organellar genome (mitochondrial DNA) within a cell or individual

Front 32

1. What is gonadal mosaicism?

Back 32

1. mosaicism that results from a mutation postzygotically during early (embryonic) development. It effects only cells destined to form the gonads. So somatic cells are unaffected, but the gametes carry the mutation

Front 33

1. What are prominent manifestations of Down's other than mental retardation?

Back 33

1. Congenital heart disease, risk of leukemia, Alzheimer like disease