Clinical Correlates

Question 1

Xeroderma Pigmentosum

Answer 1

Error in NER. Photosensitivity, and frequent skin breaks.

Question 2

Hereditary Nonpolyposis Colorectal Cancer

Answer 2

AKA “Lynch Syndrome”. Error in MMR causing micro-satellite instability

Question 3

High Risk of breast or ovarian Cancer

Answer 3

Defects in BRCA1 or BRCA2. Both used in homologous recombination.

Question 4

I-Cell Disease

Answer 4

Deficiency in phosphotransferase for mannose6 tagging for lysosomal enzymes. Enzymes secreted into body.

Question 5

Swyer Syndrome

Answer 5

Mutation in NLS of sex determining region of Y chromosome protein. XY individuals born as phenotypic females.

Question 6

Human Deafness dystonia Syndrome

Answer 6

Defect in deafness, dystonia protein located within TIM complex. X-linked recessive. Progressive deafness, blindness, dystonia, dysphagia.

Question 7

Zellweger’s syndrome

Answer 7

Inability to target proteins to matrix of peroxisomes. AR. Neuro impairment = death around 1 year old.

Question 8

Congenital Disorders of glycosylation

Answer 8

Defect in synthesis of N-linked proteins due to 1)Defect in synthesis or transfer of oligosacch(ER) or 2) Modification reactions (Golgi)

Question 9

Scurvy

Answer 9

Collagen disorder: Acquired due to vit D deficiency. Fragile blood vessels and skin, loose teeth.

Question 10

Osteogenesis Imperfecta

Answer 10

Collagen Disorder: “Brittle Bone disease”. Genetic. Synthesis of shorter or longer collagen chains or replacement of glycine.

Question 11

Ehlers Danlos Syndrome

Answer 11

Collagen Disorder: Genetic. Skin extensibility and fragility. Joint hyper-mobility. Mostly due to COL gene defect. Occasionally due to defect in collagen processing enzyme (Lysyl hydroxylase)

Question 12

Tay-Sachs

Answer 12

Frameshift mutation (4bp insertion). Common in Ashkenazi Jewish Patients.

Question 13

Cystic Fibrosis

Answer 13

3 bp deletion. Lost residue prevents normal folding.

Question 14

B-Thalassemia

Answer 14

G to A mutation at position 110 on 1st intron –> Abnormal Splice acceptor site. 90% mRNA generated at incorrect splice site.

Question 15

Hemophilia B

Answer 15

X linked clotting disease. Mutation in 5’ UTR. 1/3 amount of clotting activity.

Question 16

Trinucleotide repeat Diseases

Answer 16

Huntgington(coding), Kennedy(coding), Fragile X(5’UTR), Mytonic dystrophy(3’UTR)

Question 17

Alpha Thalassemia

Answer 17

Complete/partial Gene deletion with high carrier rate.

Question 18

Charcot-Marie Tooth Disease

Answer 18

Duplication of PMP22 gene. Causes demyelination of CMT and atrophy of distal limb muscles.

Question 19

Chronic Myelogenous Leukemia

Answer 19

Reciprocal Translocation (9+22 philadelphia Chromosome).

Question 20

Retrotransposons

Answer 20

Thought to be the basis of rare cases of hemophilia A and Duchenne Muscular Dystrophy

Question 21

Steroid/nuclear Receptors

Answer 21

Ex. Estrogen Receptor. Over-expressed in subset of breast cancers, driving expression of genes that promote growth and survival of breast cancer cells.

Question 22

Lesch-Nyan SYndrome

Answer 22

HGPRT activity <1.5% normal. Causes increased PRPP and uric acid. Signs: Hyperuricemia w/gout, self mutilation, neuro abnormalities.

Question 23

Severe combined immunodeficiency Syndrome

Answer 23

“SCIDS”. Decreased # and function of T and B lymphocytes. Cause: Adenosine deaminase deficiency leading to developmental arrest or apoptosis of lymphocytes.

Question 24

Orotic Aciduria

Answer 24

Inherited AR disorder or pyrimidine de novo synthesis. UMP synthase activities are deficient. Signs: Failure to grow and develop.

Question 25

Gout

Answer 25

Inflammatory arthritis: Chronic hyperuricemia, MSU in tissues, and significant inflammation. Primarily caused by under secretion of urate. Treatment: Address inflammation, lower urate in tissues.