Clinical Correlates Flashcards
Xeroderma Pigmentosum
Error in NER. Photosensitivity, and frequent skin breaks.
Hereditary Nonpolyposis Colorectal Cancer
AKA “Lynch Syndrome”. Error in MMR causing micro-satellite instability
High Risk of breast or ovarian Cancer
Defects in BRCA1 or BRCA2. Both used in homologous recombination.
I-Cell Disease
Deficiency in phosphotransferase for mannose6 tagging for lysosomal enzymes. Enzymes secreted into body.
Swyer Syndrome
Mutation in NLS of sex determining region of Y chromosome protein. XY individuals born as phenotypic females.
Human Deafness dystonia Syndrome
Defect in deafness, dystonia protein located within TIM complex. X-linked recessive. Progressive deafness, blindness, dystonia, dysphagia.
Zellweger’s syndrome
Inability to target proteins to matrix of peroxisomes. AR. Neuro impairment = death around 1 year old.
Congenital Disorders of glycosylation
Defect in synthesis of N-linked proteins due to 1)Defect in synthesis or transfer of oligosacch(ER) or 2) Modification reactions (Golgi)
Scurvy
Collagen disorder: Acquired due to vit D deficiency. Fragile blood vessels and skin, loose teeth.
Osteogenesis Imperfecta
Collagen Disorder: “Brittle Bone disease”. Genetic. Synthesis of shorter or longer collagen chains or replacement of glycine.
Ehlers Danlos Syndrome
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)
Tay-Sachs
Frameshift mutation (4bp insertion). Common in Ashkenazi Jewish Patients.
Cystic Fibrosis
3 bp deletion. Lost residue prevents normal folding.
B-Thalassemia
G to A mutation at position 110 on 1st intron –> Abnormal Splice acceptor site. 90% mRNA generated at incorrect splice site.
Hemophilia B
X linked clotting disease. Mutation in 5’ UTR. 1/3 amount of clotting activity.
Trinucleotide repeat Diseases
Huntgington(coding), Kennedy(coding), Fragile X(5’UTR), Mytonic dystrophy(3’UTR)
Alpha Thalassemia
Complete/partial Gene deletion with high carrier rate.
Charcot-Marie Tooth Disease
Duplication of PMP22 gene. Causes demyelination of CMT and atrophy of distal limb muscles.
Chronic Myelogenous Leukemia
Reciprocal Translocation (9+22 philadelphia Chromosome).
Retrotransposons
Thought to be the basis of rare cases of hemophilia A and Duchenne Muscular Dystrophy
Steroid/nuclear Receptors
Ex. Estrogen Receptor. Over-expressed in subset of breast cancers, driving expression of genes that promote growth and survival of breast cancer cells.
Lesch-Nyan SYndrome
HGPRT activity <1.5% normal. Causes increased PRPP and uric acid. Signs: Hyperuricemia w/gout, self mutilation, neuro abnormalities.
Severe combined immunodeficiency Syndrome
“SCIDS”. Decreased # and function of T and B lymphocytes. Cause: Adenosine deaminase deficiency leading to developmental arrest or apoptosis of lymphocytes.
Orotic Aciduria
Inherited AR disorder or pyrimidine de novo synthesis. UMP synthase activities are deficient. Signs: Failure to grow and develop.
Gout
Inflammatory arthritis: Chronic hyperuricemia, MSU in tissues, and significant inflammation. Primarily caused by under secretion of urate. Treatment: Address inflammation, lower urate in tissues.
