Diseases for Cell Biology D

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Rep

air

Def

ects

Disease Heritance Clinical Manifestation Gene/Protein Affected Function Affected Xeroderma pigmentosum AR Cutaneous photosensitivity to UV

radiation Nucleotide excision repair proteins (point mutation)

Genome-wide nucleotide excision repair

Cockaynes AR Poor growth, neurological degeneration, early senility

Nucleotide excision repair proteins

Transcription-coupled nucleotide excision repair

HNPCC AD Cancer susceptibility, susceptible to UV radiation

Mismatch repair proteins Post-replication mismatch repair

Ataxia-telangiectasia AR Motor incoordination, immune deficiency, chromosomal breaks, lymphomas (-radiation)

Protein kinase activated by DNA double-strand breaks

Cell cycle arrest after DNA breakage, genomic instabilty

Blooms AR Poor growth, butterfly rash, immunodeficiency, cancer susceptibility, chromosome breaks

DNA helicase Chromosomal repair due to alkylating agents

Werners AR Early senility DNA helicase, exonuclease Unknown Fanconi Anemia AR Anemia, leukemia, skeletal deformities,

chromosome breakage Heterogenous at least 8 diff. proteins

Crosslink-repair

Breast cancer susceptibility

AR Breast and ovarian cancer BRCA1&2, interacts with repair enzymes

Recombinational repair, transcription-coupled repair of oxidative damage

Spinocerebellar ataxia AD,AR,XR Motor incoordination Heterogenous Repair or single-strand breaks

Mit

ocho

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isea

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MERRF Generalized muscle weakness, ataxia, seizures, respiratory & cardiac failure

tRNALys, oxidative phosphorylation complexes I & IV

Oxidative phosphorylation; muscles and neurons most affected

Lebers Hereditary Optic Neuropathy

Delayed bilateral vision loss, distended capillaries around optic nerve, optic atrophy

Electron transport Oxidative phosphorylation

Lyso

som

al S

tora

ge

Dis

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I-Cell Disease Coarse facial features, skeletal abnormalities, mental retardation

GNPTA gene, UDP-N-acetylglucosamine-1-phosphotransferase

Failure of mannose-6-phosphate tagging of lysosomal enzymes directs them to cell membrane

Pompe Disease Lysosomal glucosidase Glycogen metabolism Tay-Sachs Disease Mental retardation, death Hexosaminidase A GM2 ganglioside metabolism Gaucher Disease Glucocerebrosidase Glucocerebroside metabolism Neimann-Pick Disease Sphingomyelinase Sphingomyelin metabolism Hurler Syndrome -L-Iduronidase Heparan and dermatan SO4 metabolism

Pero

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Dis

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X-Linked Adrenoleukodystrophy

XR Peroxisomal enzymes Insufficient fatty acid metabolism, deterioration of myelin sheath

Zellweger Syndrome AR PXR1 receptor Inability to import proteins into peroxisome, rendering them incapable of function

Cilia

Dis

ease

s

Heterotaxia Cilia Nodal flow Retinal degeneration Cilia Photoreception Anosmia Cilia Odorant reception Polycystic Kidney Disease Cilia Mechanosensation Polydactyly Cilia Gli repressor formation Neural patterning defects Cilia Gli repressor or activator formation Neural tube closure defects

Cilia Convergent extension

Kartageners Syndrome Permanent bronchodilation (bronchiectasis), male sterility, chronic rhinitis, sinusitis

Cilia Inability to move

IFs Epidermolysis Bullosa Simplex (EBS) Skin blisters after minor trauma Keratin genes 5, 14 Abnormal assembly of keratin filaments

Progeria Premature aging Nuclear lamins Poor re-formation of nucleus after cell division, poor chromatin binding

Oth

er G

enet

ic D

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ses

Gout Buildup of uric acid crystals at joints Xanthine oxidase Error in adenylate metabolism Downs Syndrome Mental retardation, physical defects Trisomy-21 Overexpression (1.5x) of genes on chromosome 21 Fragile-X Syndrome Mental retardation in males RNA-binding protein in

RISC complex Defect in translation repression

SCIDS Susceptibility to opportunistic infections

Adenosine deaminase Inability to metabolize adenosine to hypoxanthine

Marfan Syndrome AD Arachnodactyly, aortic rupture, retinal detachment, increased height and limb length, myopia, mitral valve prolapse

Fibrillin-1 Weak and unstable connective tissue

Oculocutaneous albinism AR Absence of pigment in hair, skin, and eyes, nystagmus, photophobia, reduced vision

Melanin, tyrosinase Tyrosine DOPA dopaquinone melanin pathway

Duchennes Muscular Dystrophy

XR Lack of coordination, muscle pseudohypertrophy (esp. in calves), elevated CK levels

Dystrophin Improper growth of muscles

Osteogeneis imperfect AD Frequent fractures in young children Collagen Failure to incorporate collagen or use of mutant collagen in connective tissue Neurofibromatosis-1 AD Caf-au-lait spots, fibrous skin tumors NF1 tumor suppressor

gene Tumor suppression

Myotonic dystrophy Complex Muscle wasting beginning in face and hands, myotonia (inability to relax post contraction)

Triple repeats (CTG) in myotonin gene

Repeat expansion occurring in female meiosis rendering myotonin gene inactive

Prader-Willi Syndrome Imprinted (Paternal)

Diminished fetal activity, muscular hypotonia, mental retardation, short stature, hypogonadia, hyperphagia

Chr-15 deletion Good at jigsaw puzzles for some reason

Angelman Syndrome Imprinted (Maternal)

Severe motor and intellectual retardation, ataxia, hypotonia, epilepsy, lack of speech, large jaw

Chr-15 deletion (same as Prader-Willi)

Happy puppet syndrome due to excessive laughter, jerky movement