Genetic Disorders

Question 1

genome mutation

Answer 1

whole chromosome

Question 2

chromosome mutation

Answer 2

visible chromosome change (e.g. deletion, transloctation)

Question 3

gene mutation

Answer 3

may, and often result in single base error

Question 4

fragile X syndrome

Answer 4

trinucleotide repeat (CGG)

Question 5

autosomal dominant disease characteristics

Answer 5

1. reduced penetrance
2. variable expressivity
3. delayed onset
4. reduced production or inactive protein
5. both sexes involved
6. no skipping of generations

Question 6

autosomal recessive disease characteristics

Answer 6

1. complete penetrance
2. uniform expression
3. early in life
4. loss of function proteins
5. much more common than AD, include ALL inborn errors of metabolism
6. both sexes involved
7. skipping of generations

Question 7

sex (X)-linked characteristics

Answer 7

only males affected, daughters are carriers

Question 8

sex-linked recessive disorders

Answer 8

Duchenne muscular dystrophy, hemophilia A and B, G6PD deficiency, agammaglobinemia, Wiskott-Aldrich syndrome, diabetes insipidus, Lesch-Nyhan syndrome, fragile X syndrome, chronic granulomatous disease

Question 9

Marfan syndrome

Answer 9

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

Question 10

Ehlers-Danlos syndrome

Answer 10

AD, AR
collagen defects, 6 types
hyperelastic skin, hyperextensible joints, poor wound healing

Question 11

familial hypercholersterolemia

Answer 11

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

Question 12

lysosomal storage disease

Answer 12

comprise most of enzyme deficiencies

1. glycogen storage diseases
2. sphingolipidoses
3. sulfatidoses
4. mucopolysaccharidoses
5. mucolipidoses

Question 13

glycogen storage diseases

Answer 13

buildup of glycogen in liver, muscle, heart

1. Type 2 (Pompe)
2. von Gierke
3. McArdle

Question 14

Tay-Sach’s diseases

Answer 14

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

Question 15

sulfatidoses

Answer 15

Buildup of sulfatides, cerebrosides, and sphingomyelin

1. metachromatic leukodystrophies (CNS)
2. Krabbe
3. Fabry
4. Gaucher
5. Niemann-Pick (A and B)

Question 16

Niemann-Pick A and B

Answer 16

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

Question 17

Gaucher disease

Answer 17

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

Question 18

mucopolysaccharidoses

Answer 18

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

Question 19

alcaptonuria

Answer 19

Buildup of homogentisic acid
Not a lysosomal storage disease
Black urine
Black nails
Black joint cartilage

Question 20

neurofibromatosis

Answer 20

AD, 1- von Recklinghausen, 2- accoustic neurofibromatosis

1: neurofibromas, cafe-au-lait spots, Lisch nodules
2. b/l accoustic neuromas, meningiomas

Question 21

trisomies

Answer 21

21 (Down’s), 8, 9, 13 (Patau), 18 (Edward’s), 22

Question 22

trisomy 21

Answer 22

Down’s syndrome
Maternal age-related
Most common cause of mental retardation
Congenital heart defects, risk for acute leukemias, GI atresias

Question 23

22q11.2 deletion

Answer 23

Detected by FISH

Cardiac defects, DiGeorge syndrome, velocardiofacial

Question 24

sex chromosome disorders

Answer 24

Problems related to sexual development and fertility
Discovered at puberty
Retardation related to number of X chromosomes
At least 1 Y chromosome = male

Question 25

Klinefelter syndrome

Answer 25

XXY, XXXY, etc.
Hypogonadism at puberty
#1 cause male infertility
No retardation unless multiple Xs
Long legs, atrophic testes, small penis

Question 26

Turner syndrome

Answer 26

45X
Mosaicism common
Streak gonads
Neck webbing
Edema of hand dorsum
Congenital heart defects

Question 27

autosomal dominant disorders

Answer 27

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

Question 28

autosomal recessive disorders

Answer 28

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

Question 29

Nieman Pick C

Answer 29

Mutations in NPC1 or NPC2 > defective cholesterol transport
Buildup of cholesterol and gangliosides in nervous system
Ataxia, dysarthria, psychomotor regression