Diseases II

Question 1

Junctional Epidermolysis Bullosa

Answer 1

homozygous defect in LAMB3 gene; example of Somatic mosaicism due to a intragenic 2nd site suppressor mutation

Question 2

Hereditary non-polyposis colon cancer (HNPCC; Lynch disease)

Answer 2

Autosomal dominant; defect in mismatch repair genes causing early non-polyposis colon cancer

Question 3

Hemophilia A

Answer 3

disruption of Factor VIII by L1, a TGE-like DNA element

Question 4

Aicardi-Goutieres syndrome

Answer 4

neurodevelopmental disorder associated with defects in genes coding for Rnase H2

Question 5

Xeroderma pimentosum

Answer 5

defect in nucleotide excise repair causing extreme photosensitivity and early skin cancer

Question 6

Cockayne syndrome

Answer 6

defect in transcription-coupled repair leading to neurodevelopmental disorders and premature aging

Question 7

Trichothiodystrophy

Answer 7

defect in transcription-coupled repair leading to “brittle hair”; little cancer disposition

Question 8

Bloom syndrome

Answer 8

Autosomal recessive; defect in recombination pathway (DSB) leading to photosensitivity, growth arrest, and cancer susceptibility

Question 9

Werner syndrome

Answer 9

Autosomal recessive; defect in recombination pathway (DSB) leading to premature aging and cancer susceptibility

Question 10

Li-Fraumeni syndrome

Answer 10

defect in p53 (DNA damage response) causing high predisposition to cancer

Question 11

Xeroderma pimentosum variant

Answer 11

defect in DNA polymerase Eta causing extreme photosensitivity and early skin cancer

Question 12

Myoclonic Epilepsy associated with Ragged Red Fibers (MERRF)

Answer 12

mutation in mitocondrial tRNA genes

Question 13

Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes (MELAS)

Answer 13

mutations in mitochondrial tRNA and NAD dehydrogenase genes

Question 14

Leber Hereditary Optic Neuropathy

Answer 14

mutations in mitochondrial NAD dehydrogenase genes

Question 15

Cystic Fibrosis

Answer 15

autosomal recessive disease; defect in CFTR (chloride ion channel), most common is delta F508 -> proteosome degrades protein before reaching the membrane

Question 16

Duchene/Becker muscular dystrophy

Answer 16

X-linked recessive; deletion or nonsense mutation in dystrophin gene; 1/3 de novo mutations; frame shift hypothesis

Question 17

Fragile X syndrome

Answer 17

X-linked dominant; repeated CGG in 5’ UTR of FMR-1 gene; 50-100 pre-mutation; pre-mutation males never have affected daughters

Question 18

Myotonic dystrophy

Answer 18

autosomal dominant; repeated CTG in 3’ UTR of DM-1 or CCTG repeats in 1st intron of DM-2; gain of function toxic mRNA; 40 repeats has symptoms; anticipation

Question 19

Huntington’s disease

Answer 19

autosomal dominant; repeated CAG in ORF of HD gene; > 40 repeats have earlier onset; anticipation; strand slippage

Question 20

Kennedy disease

Answer 20

X-linked recessive; repeated CAG in 1st exon of androgen receptor gene; toxic gain of function

Question 21

XY females

Answer 21

loss of function of androgen receptor gene

Question 22

Trisomy 21

Answer 22

94-95% simple disomy; epicanthal folds, upslanting palpebrae, septal heart defects

Question 23

Trisomy 18

Answer 23

Intrauterine growth retardation, bird-like facies, rocker bottom feet, clenched fists

Question 24

Trisomy 13

Answer 24

intrauterine growth retardation, holoprosencephaly, oro-facial clefts, polydactyly

Question 25

DiGeorge/velocardiofacial syndrome

Answer 25

very commonly a 22q11.2 deletion; hypocalcemia, immunodeficiency, contruncal heart defects

Question 26

Turner syndrome (X0)

Answer 26

short stature, ovarian dysgenesis (infertility), webbed neck

Question 27

Klinefelter syndrome (XXY)

Answer 27

infertility, gynecomastia, mild learning disabilities

Question 28

XXX

Answer 28

normal physical features and fertility, mild learning disabilities with increased risk of psychiatric disorders

Question 29

XYY

Answer 29

tall stature, normal fertility, mild learning disabilities

Question 30

Thrombophilia

Answer 30

predisposition genes - Factor V Leiden (failed to be inactivated) and Prothrombin (more stable mRNA)

Question 31

Long QT syndrome

Answer 31

mutations in sodium, potassium channel (LQT1-3,5,6) causing slow repolarization of membrane

Question 32

Hypertrophic cardiomyopathy

Answer 32

common cause of sudden death in young adults; mutation in cardiac contractile proteins (MYBPC3 and MYH7)

Question 33

Alzheimer’s disease

Answer 33

early onset caused by mutation in APP, presenilin 1, and presenilin 2; late onset caused by variants of ApoE (E2- protective, E3- neutral, E4- 4x risk)

Question 34

Obesity and TIID

Answer 34

dysregulation of fat and sugar metabolism; leptin -> produced in adipocytes and cause cells to expend energy stores and ingest less