Genetic Disorders

Question 1

Trisomy 21

Answer 1

epicanthic folds, simian crease, congenital heart defects, prone to leukemia, early onset Alzheimer

Question 2

Patau Syndrome

Answer 2

3 copies of chromosome 13

cleft lip, cardiac and renal defects, micropthalmia, microcephaly, mental retardation

Question 3

Edwards Syndrome

Answer 3

three copies of chromosome 18

micrognathia, overlapping fingers, horseshoe shaped kidneys, prominent occiput

Question 4

Fragile X Syndome

Answer 4

caused by long repeating sequences of three nucleotides
long face, large mandible, large everted ears, large testicles, sometimes mental retardation
*get anticipation between generations

Question 5

Huntington Disease

Answer 5

CAG repeats in first exon of HTT gene; “gain of function,” AD
leads to production of a toxic protein causing neuronal death
leads to movement disorder and dementia

Question 6

Hereditary Hematochromatosis

Answer 6

AR caused by excessive iron absorption - leads to fibrosis and liver cirrhosis
cause use restriction enzymes after PCR because the mutation is in an RE site

Question 7

Marfan Syndrome

Answer 7

AD, caused by mutations in FBN1 and 2 genes and leads to the mutant fibrillin-1 protein which causes loss of structural support in microfibril rich reagions and the increase of TGFbeta signaling
symptoms: long extremities and tall, flexible joints, spinal and chest deformities, cardiovascular lesions, dilation of ascending aorta

Question 8

Turner Syndrome

Answer 8

X monosomy (can be due to mosaicism or genetic loss of some other kind) leads to short stature, failure of secondary sex characteristic development, atrophy of ovaries, edema and neck swelling - leads to webbed neck later on

Question 9

Klinefelter Syndrome

Answer 9

XXY, phenotypically male, hypogonadism, infertility, eunichoid appearance, increased estrogen, low testosterone, gynecomastia, failure of secondary sex characteristics to develop

Question 10

Ehlers Dantos Syndromes

Answer 10

a group of diseases dealing with defective collagen
1. can have AR mutation where you don’t have lysyl hydroxylase which prevents collagen cross-linking
2. you can have AD mutation in type III collagen which causes a dominant negative effect
Symptoms: hyperextensible, vulnerable to trauma, rupture of large arteries

Question 11

Familial Hypercholesterolemia

Answer 11

Mutation in the LDL receptor, get elevated levels of cholesterol which increases artherosclerosis or possibility of cardiovascular events
xanthomas common
Class II is most common: abnormal LDL receptor folding leads to accumulation in ER

Question 12

Lysosomal Storage Disorders (in general)

Answer 12

genetic deficiency in lysosomal enzymes
mutations can affecting targeting enzymes for lysosome via mannose-6-phosphate - metabolites accumulate in lysosome
organs with lots of macrophages are affected (spleen, liver)

Question 13

Tay Sach’s Disease

Answer 13

mutation: hexosaminidase
accumulation: gangliosides
clinical: motor and mental deterioration, blindness, neuronal destruction

Question 14

Niemann-Pick Disease Type A and B

Answer 14

mutation: sphingomyelinase
accumulation: sphingomyelin
clinical:
A - severe, diffuse CNS involvement, early death, hepatosplenomegaly
B - less severe, no CNS involvement

Question 15

Niemann-Pick Disease Type C

Answer 15

mutation in NPC1 or NPC2 gene which causes accumulation of cholesterol and gangliosides
leads to hydrops fetalis, neonatal hepatitis, and neurologic disorder

Question 16

Gaucher Disease

Answer 16

deficiency in glucocerebrosidases, accumulation of glucocerebrosides
Clinical: hepatosplenomegaly
Type I - no neuronal involvement
Type II - immediate neuronal involvement, death in childhood
Type III intermediate between I and II, CNS involvement manifests in adolescence

Question 17

Mucopolysaccharidoses

Answer 17

a group of disorders resulting from deficiency in enzymes that break down glycosaminoglycans

clinical: coarse facial features, corneal clouding, arterial thickening, mental retardation
* **Clear Cytoplasm is HUGE hint

Question 18

Hurler Syndrome

Answer 18

a type of mucopolysaccharidosis

due to alpha-1-iduronidase deficiency - early death due to cardiovascular complications

Question 19

Von Gierke Disease

Answer 19

hepatic form of glycogen storage disease due to glucose-6-phosphate deficiency
get hypoglycemia and glycogen accumulation

Question 20

McArdle Disease

Answer 20

a myopathic form of glycogen storage disorder resulting from muscle phosphorylase deficiency
causes muscle weakness and cramping post-exercise

Question 21

Pompe DIsease

Answer 21

whole body glycogen storage disorder resulting from deficiency in acid maltase/alpha glucosidase
causes early death

Question 22

Alkaptonuria/Ochronosis

Answer 22

AR, lack of homogentisic oxidase leads to phenylalanine and homogentisic acid buildup
dark urine, ochronosis

Question 23

DiGeorge Syndrome

Answer 23

Chromosome 22q11.2 deletion causing T cell immunodeficiency and hypocalcemia

Question 24

Velocardiofacial Syndrome

Answer 24

Chromosome 22 deletion causing facial dysmorphology and cardiac malformations

Question 25

Prader Willi Syndrome

Answer 25

paternal 15q12 region is deleted leaving behind only the silenced maternal gene
mental retardation, short stature, obesity, hypogonadism

Question 26

Angelman Syndrome

Answer 26

maternal 15q12 region is deleted, leaving behind only silenced paternal gene
mental retardation, ataxia, inappropriate laughter, seizures
**gene codes for unbiquitin