Genetics in Medicine Presentation information

Adenosine Deaminase Deficiency (ADA-SCID)

Autosomal recessive

Little to no immune system

ADA

Adenosine deaminase; housekeeping enzyme

Purine salvage; uric acid breakdown

Most are missense mutations

Uric acid is built up

Marfan Syndrome

Autosomal dominant

Weakened connective tissue

FBN-1

Fibrillin-1; structural protein in microfibrils

TGF-ß accumulation

Missense of G -> A

Microfibrils sequester TGF-ß

Duchenne Muscular Dystrophy

X-Linked recessive

Delayed development, dystrophy

DMD

Dystrophin; stabilizes muscle membranes

Stability of microtubules

Mostly deletions (exon 44)

Lack of stability, cell damage, stress

Tay-Sachs

Autosomal recessive

Neurodegeneration; red spot on macula

HEXA

Lysosomal hexosaminidase; degrades lipids

Cleavage of GalNac from Gm2

Many kinds, LOF; insertion/deletion?

Buildup of Gm2 ganglioside

Miller-Dieker

DE NOVO

Lisssencephaly (smooth brain)

Deletion of chr. 17; (PAFAH1B1)

Dynein; nuclear translocation

LIS1/Dynein

Many kinds

Impeded nuclear translocation

Trimethylaminuria

Autosomal recessive

Rotten fish odor in bodily fluids

FMO3

Flavin-containing monooxygenase 3; converts TMA to TMAO

Missense of G -> T transversion; termination

No TMAO produced; may be good

Retinitis Pigmentosa

Focus on Auto. Dom.

Damage to photoreceptor cells

NR2E3

NR2E3; differentiation of rods and cones in development

Altered dimerization

Many; Missense in exon 2 (G -> A or C)

Unable to form homodimers

Methemoglobinemia

Autosomal recessive

Cyanosis

CYTB5R

NADH-cytochrome B5 reductase; reduction of methemoglobin to hemoglobin

Methemoglobin reduction

Deletion mutation of entire codon; unable to bind oxygen

Too much methemoglobin

Lesch-Nyhan

X-Linked recessive

Gout, renal, self-harm

HPRT1

HGPRT; recycles guanine and hypoxanthine

Purine degradation; overproduction of uric acid

Nonsense, frameshift, missense

Overproduction of uric acid

Hemophilia A

X-Linked recessive / de novo

Difficulty in clotting

F8

Factor VIII; creates fibrin from fibrinogen

Clotting cascade and hemostasis

Translocation, missense and nonsense

Instability in the clot, continuous bleeding

Hereditary Breast & Ovarian cancer

Autosomal dominant

Cancer!

BRCA1

E3 Ubiquitin ligase; degradation

Ubiquitination

Many mutations bc many genes susceptible

Inability to break down proteins

Zellweger syndrome

Autosomal recessive

Liver dysfunction, facial abnormalities

PEX1

Peroxin; generation of peroxisomes

Stops everything

Null

Inability to hydrolyze ATP, shuts down entire pathway

Sickle Cell Anemia

Autosomal recessive

Endothelial dysfunction

HBB

ß-globin subunit of hemoglobin; production of functional hemoglobin

Hb polymerization

Point mutation; substitution (T to A)

HbS is polymerized instead

Huntington’s

Autosomal dominant

Atrophy and reduced white matter; cognitive and motor

HTT

Huntington protein; protein-protein interactions

Protein folding

Super repeats; toxic GOF mutation

Elongated protein, altered folding

Glucose 6-phosphate deficiency

X-Linked recessive / dominant

Upper abdominal pain, jaundice, fever, dark urine

G6PD

Converts G6P to 6-phosphogluconate

Oxidative pentose phosphate pathway

Missense; Viangchan

Loss of efficiency, buildup of reactants

Myoclonic Epilepsy with Ragged Red Fibers

Maternal-Inherited

Epilepsy and brain atrophy

tRNA gene in mitochondrial DNA

T and D loop interactions; protein structure

Production of functional proteins and ETC

Point mutation possible

Failure

Ehlers-Danlos (!!)

Autosomal dominant

Fragile skin, hypermobility, difficulty in wound healing

COL5A1

Collagen; structural protein in connective tissue

Formation of collagen fibrils

Nonsense transversion; truncation

Weakened fibrils