Genetic Disorders Flashcards
genome mutation
whole chromosome
chromosome mutation
visible chromosome change (e.g. deletion, transloctation)
gene mutation
may, and often result in single base error
fragile X syndrome
trinucleotide repeat (CGG)
autosomal dominant disease characteristics
- reduced penetrance
- variable expressivity
- delayed onset
- reduced production or inactive protein
- both sexes involved
- no skipping of generations
autosomal recessive disease characteristics
- complete penetrance
- uniform expression
- early in life
- loss of function proteins
- much more common than AD, include ALL inborn errors of metabolism
- both sexes involved
- skipping of generations
sex (X)-linked characteristics
only males affected, daughters are carriers
sex-linked recessive disorders
Duchenne muscular dystrophy, hemophilia A and B, G6PD deficiency, agammaglobinemia, Wiskott-Aldrich syndrome, diabetes insipidus, Lesch-Nyhan syndrome, fragile X syndrome, chronic granulomatous disease
Marfan syndrome
AD
FBN1 gene mutation > fibrillin defect
Fibrillin needed for CT structural integrity and TGF-beta signaling
Affects skeleton, eye, and CV system
Tall, long fingers, b/l lens subluxation, mitral valve prolapse, aortic aneurysms and disections
Abe Lincoln
Ehlers-Danlos syndrome
AD, AR
collagen defects, 6 types
hyperelastic skin, hyperextensible joints, poor wound healing
familial hypercholersterolemia
AD
LDL receptor defect > hypercholesterolemia
Heterozygotes: increased risk of atherosclerosis and coronary artery disease
Homozygotes: higher serum cholesterol, higher frequency of ischemic heart disease
Xanthomas of tendon sheaths
Scavenger system > foamy macrophages
lysosomal storage disease
comprise most of enzyme deficiencies
- glycogen storage diseases
- sphingolipidoses
- sulfatidoses
- mucopolysaccharidoses
- mucolipidoses
glycogen storage diseases
buildup of glycogen in liver, muscle, heart
- Type 2 (Pompe)
- von Gierke
- McArdle
Tay-Sach’s diseases
Sphingolipidosis Ashkenazi Jews Deficient alpha-subunit of hexosamidase Accumulation of GM2 gangliosides in CNS neurons, ANS, and retina Cherry red spot in macula Death by 2-3 yrs
sulfatidoses
Buildup of sulfatides, cerebrosides, and sphingomyelin
- metachromatic leukodystrophies (CNS)
- Krabbe
- Fabry
- Gaucher
- Niemann-Pick (A and B)
Niemann-Pick A and B
Deficient sphingomyelinase > buildup of sphingomyelin Vaculation and ballooning of neurons Cherry red spot in macula 1/3 of cases Ashkenazi Jews Massive splenomegaly Type A fatal first 3 yrs
Gaucher disease
AR
Mutated glucocerebrosidase
Accumulation of glucocerebroside
99% type I (no CNS involvement)
Foamy macrophages in spleen, liver, bone marrow, lymph nodes, tonsils, thymus, and Peyer patches
Fibrillary cytoplasm
Cerebral involvement: Gaucher cells in Virchow-Robin spaces
mucopolysaccharidoses
AR
Hurler (I) and Hunter (II)
Buildup of GAGs, dermatan sulfate, and heparan sulfate
Urinary excretion of sulfates
Course facial features, clouding of cornea, joint stiffness, mental retardation
alcaptonuria
Buildup of homogentisic acid Not a lysosomal storage disease Black urine Black nails Black joint cartilage
neurofibromatosis
AD, 1- von Recklinghausen, 2- accoustic neurofibromatosis
1: neurofibromas, cafe-au-lait spots, Lisch nodules
2. b/l accoustic neuromas, meningiomas
trisomies
21 (Down’s), 8, 9, 13 (Patau), 18 (Edward’s), 22
trisomy 21
Down’s syndrome
Maternal age-related
Most common cause of mental retardation
Congenital heart defects, risk for acute leukemias, GI atresias
22q11.2 deletion
Detected by FISH
Cardiac defects, DiGeorge syndrome, velocardiofacial
sex chromosome disorders
Problems related to sexual development and fertility
Discovered at puberty
Retardation related to number of X chromosomes
At least 1 Y chromosome = male
Klinefelter syndrome
XXY, XXXY, etc. Hypogonadism at puberty #1 cause male infertility No retardation unless multiple Xs Long legs, atrophic testes, small penis
Turner syndrome
45X Mosaicism common Streak gonads Neck webbing Edema of hand dorsum Congenital heart defects
autosomal dominant disorders
Huntington disease, neurofibromatosis, myotonic dystrophy, tuberous sclerosis, polycystic kidney disease, familial polyposis coli, hereditary spherocytosis, von Willebrand disease, Marfan syndrome, Ehlers-Danlos syndrome, osteogenesis imperfecta, achondroplasia, familial hypercholesterolemia, acute intermittent porphyria
autosomal recessive disorders
cystic fibrosis, phenylketonuria, galactosemia, homocysteinuria, lysosomal storage diseases, alpha-1-antitrypsin deficiency, Wilson disease, hemochromatosis, glycogen storage diseases, sickle cell anemia, thalassemias, congenital adrenal hyperplasia, Ehlers-Danlos syndrome (some variants), alkaptonuria, neurogenic muscular atrophies, Friedreich ataxia, spinal muscular atrophy
Nieman Pick C
Mutations in NPC1 or NPC2 > defective cholesterol transport
Buildup of cholesterol and gangliosides in nervous system
Ataxia, dysarthria, psychomotor regression
