Conditions

Question 1

Neurofibromatosis, type 1 (NF1)

Answer 1

AD, NF1 LOSS OF FUNCTION. neurofibromas, Lisch nodules on the iris, cafe au lait spots, axillary freckles. Optic glioma, osseous lesions. Shows variable expressivity and has a pleiotrophic phenotype and age-dependent penetrance

Question 2

congenital disorder

Answer 2

a disorder present at birth

Question 3

Congenital adrenal hyperplasia

Answer 3

Autosomal recessive. Cortisol synthesis blocked but increased synthesis of androgens. ACTH secretion increased, adrenals produce more androgens–>ambiguous genitalia, masculinization in females

Question 4

Duchenne Muscular dystrophy

Answer 4

X linked. frameshift. Loss of function mutation, deletion of dystrophin gene–>accelerated muscle breakdown.

• pseudohypertrophy of the calf
• Gower’s maneuver to stand
• weakness starts in pelvic girdle, progresses superiorly
• cardiac myopathy**

Question 5

Hereditary retinoblastoma

Answer 5

Rb gene mutation, loss of function mutation. Loss of tumor suppressor function

Question 6

Osteogenesis imperfecta type I

Answer 6

Autosomal dominant bone disorder. Nonsense mutation=premature termination of Col1A1. Reduced collagen=brittle bones, fractures, blue sclera, can be confused with child abuse

Question 7

Hemoglobin Kempsey

Answer 7

missesnse mutation of Beta hemoglobin gene. Gain of function mutation. Hemoglobin has higher affinity for oxygen, does not unload oxygen effectively in tissues.

Question 8

Achondroplasia

Answer 8

AD. FGFR3 mutation increases the normal signaling though intracellular tyrosine kinase domain (receptor always in the ‘turned-on’ state).

• Rhizomelic limb shortening, short fingers, trident hands, midface retrustion, frontal bossing, small foramen magnum, craniocervical instability
• associated with advanced paternal age

Question 9

Alzheimer disease

Answer 9

Multifactorial or Autosomal Dominant. Gain of function mutation. in Trisomy 21, extra copy of chromosome = 3 copies of the APP gene. increased production of APP protein which contributes to early-onset Alzheimer

Question 10

Charcot-Marie-Tooth

Answer 10

Autosomal Dominant. PMP22(duplication) Gain of function mutation. increases amount of PMP22 protein. degenerative nerve disorder that affects peripheral nerves and myelin sheaths.

Question 11

Sickle cell anemia

Answer 11

Autosomal recessive, novel property mutation. Glu6Val mutation of the beta globin gene= Hb that transports oxygen essentially normally. In low O2, the Val residue leads to polymerization of hemoglobin into long protein-fibers which deform and restrict RBCs

Question 12

Huntington disease

Answer 12

Autosomal dominant. Novel property mutation. triplet repeat disorder -expansion of CAG repeats in the gene increases number of glutamine residues. Above threshold = a novel toxic effect on the huntington protein

Question 13

Tay Sachs

Answer 13

AR. HEXA mutation=defective hexosaminidaseA, can’t degrade ganglioside=progressive CNS destruction.

Question 14

Achondroplasia

Answer 14

Autosomal Dominant. Mutation in FGFR3. Rhizomelic limb shortening, short fingers, genu varum, trident hands, large head/frontal bossing, midface retrusion, crainocervical instability

Question 15

What is an example of full penetrance?

Answer 15

Achondroplasia

Question 16

What are 3 examples of reduced penetrance?

Answer 16

Retinoblastoma, BRCA, Huntington’s

Question 17

What are two examples of variable expressivity?

Answer 17

neurofibromatosis Type 1, Van der Woude

Question 18

What are some of the variable expressivity traits of neurofibromatosis type 1?

Answer 18

cafe au lait spots, neurofibromas, axillary/inguinal freckles, optic glioma, lisch nodules, osseous lesions

Question 19

What causes neurofibromatosis?

Answer 19

Loss of function mutation of NF1 (neurofibromin-tumor suppressor gene)

Question 20

Marfan’s

Answer 20

Autosomal dominant, mutation in FBN1-reduces amount

Question 21

Symptoms of Marfans

Answer 21

connective tissue: occular, skeletal, cardiovascular. Aortic root enlargement, ectopia lentis, tall stature

Question 22

Autosomal Dominant Polycystic Kidney disease

Answer 22

Autosomal dominant, PKD1 and PKD2 mutations produce truncated polycystin 1 and 2. large renal cysts

Question 23

Familial hypercholesterolemia

Answer 23

Autosomal Dominant. LDLR mutation, high cholesterol and LDL, xanthomas, premature artery disease and death

Question 24

Huntington disease

Answer 24

Autosomal Dominant. Mutation of HTT protein with trinucleotide expansion of glutamine. Penetrance depends on the number of repeats. Anticipation common from generation to generation. Paternal transmission bias

Question 25

Duchenne Muscular Dystrophy

Answer 25

X linked recessive. DMD mutates, absence of dystrophin. Calf hypertrophy, muscular weakness proximal>distal, cardiomyopathy. Onset before 5, wheelchair bound by 13, death in 30s. Gower’s maneuver

Question 26

Hemophilia A

Answer 26

X linked recessive, F8 mutation, Factor 8 deficiency. Spontaneous bleeds, bruising, delayed wound healing. 10% of females affected. Treat with giving factor VIII

Question 27

Fragile X

Answer 27

Trinucleotide repeat (CGG) FMR1, silenced=failure to produce protein=mental retardation.located in 5’UTR** 1/3 females affected. dysmorphic features, autistic behaviors (biting/flapping), aggression

Question 28

syndromic deafness with retinitis pigmentosum suggests:

Answer 28

Usher (AR)

Question 29

syndromic deafness with thyroid goiter suggests

Answer 29

Pendred (AR)

Question 30

syndromic deafness with arrhythmia or sudden death suggests

Answer 30

Jervell and Lange-Nielson (AR)

Question 31

syndromic deafness with White forelock

Answer 31

Waardenburg type 1 (AD)

Question 32

syndromic deafness with 8th nerve schwannomas

Answer 32

neurofibromatosis type 2

Question 33

Androgen insensitivity

Answer 33

X linked recessive, loss of function. Mutation in androgen receptor causes feminization

Question 34

Becker Muscular dystrophy

Answer 34

X linked. exon deletion (but in frame unlike DMD), loss of function-too little dystrophin, onset later than Duchenne’s, death in 40s

Question 35

HNPP

Answer 35

AD. PMP 22 (deletion) Loss of function. focal pressure neuropathies

Question 36

Osteogenesis Imperfecta type II, III, IV

Answer 36

AD. Novel property. COL1A2. Makes malformed collagen, more severe than Type 1

Question 37

Fragile X ataxia

Answer 37

X linked. Trinucleotide repeat in 5’UTR. Too much FMRP Parkinson symptoms, ataxia/tremor

Question 38

Frederich ataxia

Answer 38

Trinucleotide repeat ** loss of function in intron

Question 39

Myotonic dystrophy 2

Answer 39

AD. Trinucleotide Repeat novel property,in intron

Question 40

PKU

Answer 40

AR mutation in phenylalanine hydroxilase mutation. Mental retardation, hyperactivity, microcephaly. Can treat with diet and BH4 cofactor

Question 41

A1-antitrypsin deficiency (ATD)

Answer 41

AR. a1-AT mutation. Too little ADT cannot inhibit elastase effectively. emphysema and liver cirrhosis
Z allele (severe): misfolded protein
S allele (less severe) unstable protein doesn't get stuck in liver

Question 42

Sandhoff

Answer 42

AR. HEXB. mutated hexoaminaseB, cannot break down globoside

Question 43

Marfan

Answer 43

AD. FBN1 mutation, loss of function-conenctive tissue disorder: tall, aortic root enlargement, ectopia lentis,

Question 44

Cooley’s anemia (_____ ______)

Answer 44

(Thalassemia major)dense skull, bone marrow, ostopenia, enlarged splen, iron overload

Question 45

Fabry disease

Answer 45

X linked. Deficiency of a-galactosidase A. Clinical: neuropathy, nephropathy, cardiomyopathy, need renal dialysis or transplantation or treat with recombinant (intracellular fairy) alpha-gal

Question 46

Pompe

Answer 46

AR, deficiency in acid a-glucosidase. progressive muscle failure unless given ERT

Question 47

Progeria

Answer 47

aging disease from lamin protein mutation. Treat with Farnesyl Transferase Inhibitor

Question 48

Nonsyndromic deafness

Answer 48

Both AD or AR (allelic heterogeneity but GJB2 is most common AR) 3/4 of hearing loss in non syndromic. conductive and neural hearing loss

Question 49

Premature ovarian failure

Answer 49

X linked triplet repeat expansion. Women only

Question 50

ADA deficiency

Answer 50

Metabolic disorder, treat with replacing intracellular protein