Genetic Disorders II

Question 1

Tx for lysosomal storage

Answer 1

enzyme replacement
substrate reduction
molecular chaperones

Question 2

tay sachs disease

Answer 2

Gm2 - gangliosidoses storage disease

common in jews of European descent

motor and mental problems - 6 months of age
blindness and death by age 2-3

progressive neuronal destruction
cherry red spot in macula

Question 3

Gm2 gangliosidose

Answer 3

tay sachs

Question 4

hexosaminidase alpha-subunit deficiency

Answer 4

tay sachs

Question 5

sphingomyelinase deficiency

Answer 5

nieman pick A and B
accumulation in sphingomyelin
common in ashrkenazic jews

type B - organomegaly - no CNS involvement - survive until adulthood

Question 6

type A niemann pick

Answer 6

more common

• manifest at birth
• death within 3 years

protuberant abdomen (hepatosplenomegaly), failure to thrive, vomiting, fever, lymphadenpaothy, psychomotor dysfunction

Question 7

Dx of nieman pickmann type A

Answer 7

liver or bone marrow Bx

-look for sphingomyelinase activity

Question 8

niemann pick type C

Answer 8

mutation in NPC1 or NPC2
-cholesterol transport

cholesterol and gangliosides Gm1 and Gm2 accumulation

hydrops fetalis, neonatal hepatitis
-progressive neuro degeneration beginning in childhood with ataxia, dystonia, psychomotor regression

Question 9

NPC1

Answer 9

mutated in nieman pick C

Question 10

gaucher disease

Answer 10

autosomal recessive
mutation in glucocerebrosidase

accumulation of glucocerebroside

type I more common - non-neuronopathic - some enzyme
type II - neuronopathic - NO enzyme - death at early age
type III - intermediated

Question 11

glucocerebrosidase

Answer 11

mutated in gaucher disease

Question 12

type I gaucher disease

Answer 12

in european jews

• non-neuronopathic
• splenomegaly and lymphadenopathy

Question 13

mucopolysaccharidoses

Answer 13

deficient enzyme that degrade glycosaminoglycans

coarse facial features, hepatosplenomegaly, corneal clouding, valve thickening, joint stiffness, mental retardation

Question 14

hurler syndrome

Answer 14

MPS 1-H
deficient alpha-1 iduronidase

onset 6-24 months
death age 6-10 (cardiovascular)

Question 15

hunter syndrome

Answer 15

MPS II

lacking corneal clouding - less severe than hurler

Question 16

von gierke disease

Answer 16

glycogen storage disease
deficient glucose 6 phosphatase
-hepatic enlargement and hypoglycemia

hepatic type - treatable - but with late complications

Question 17

mcardle disease

Answer 17

glycogen storage disease
muscle cramps after exercise, low lactate after exercise
deficient muscle phosphorylase

Question 18

pompe disease

Answer 18

glycogen storage disease
deficient acid maltase
-cardiac involvement prominent (cardiomegaly)

Question 19

alkaptonuria

Answer 19

ochronosis - blue black pigment of ears, nose, cheeks
-autosomal recessive
deficient homogentistic oxidase
blocks phenylalanine metabolism

homogentistic acid accumulation
-black color in urine

clinically evident - age 30s

Question 20

giemsa stain

Answer 20

G-banding

-to determine karyotype

Question 21

G-band organization

Answer 21

arm (p,q)
region
band
sub-band

Xp21.2

chromosome X, p arm, region 2, band 1, sub band 2

Question 22

aneuploidy

Answer 22

not an exact multiple of 3

caused by nondisjunction

and anaphase lag

Question 23

roberstonian translocation

Answer 23

results in one large and one small chromosome

Question 24

balanced reciprocal tanslocation

Answer 24

results in no net gain or loss of genetic material

Question 25

isochromose

Answer 25

one arm lost, remaining arm duplicated

Question 26

trisomy 21

Answer 26

down syndrome common 47, XY, +21 influenced in maternal age Dx: flat facies oblique palpebral fissure, epicanthic folds, simian hand creases mental retardation heart disease risk for acute leukemia live to age 47

Question 27

trisomy 18

Answer 27

``` edwards syndrome severe malformations, die within first year of life prominent occiput overlap fingers limited hip abduction ```

Question 28

trisomy 13

Answer 28

patau syndrome severe malformations, die within first year of life microcephaly umbilical hernia cleft palate and lip

Question 29

chromosome 22q11.2 deletion syndrome

Answer 29

digeorge syndrome -T cell deficiency and hypocalcemia | velicardiofacial syndrome - heart defect, facial dysmorphism, palate abnormalities,

Question 30

lyons hypothesis

Answer 30

only one X chromosome is active

Question 31

Y gene

Answer 31

has SRY | -determines testicle formation

Question 32

klinefelter syndrome

Answer 32

47XXY male hypogonadism -elongated body -reduced spermatogenesis - infertility nondisjunction during meiosis

Question 33

turner syndrome

Answer 33

``` monosomy of X -hypogonadism in females 45X neck webbing heart disease failure to develop secondary sex characteristics ``` short stature and amennorhea

Question 34

true hermaphrodite

Answer 34

both testicular and ovarian tissue | most 46XX

Question 35

female pseudohermaphrodites

Answer 35

46, XX normal ovaries and internal genitalia ambiguous external genitalia steroid exposure during gestation

Question 36

male pseudohermaphrotdites

Answer 36

gonads are testes -external genitalia are female or ambiguous due to androgen insensitivity complete testicular feminization

Question 37

fragile X syndrome

Answer 37

trinucleotide repeat mutation familial mental retardation FMR-1 gene mental retardation and enlarged testicles elongated face, large mandible

Question 38

FMR -1 gene

Answer 38

fragile X syndrome

Question 39

47XXY

Answer 39

klinefelter

Question 40

monosomy X

Answer 40

turner

Question 41

edwards

Answer 41

trisomy 18

Question 42

patau

Answer 42

trisomy 13

Question 43

leber hereditary optic neuropathy

Answer 43

bilateral loss of central vision - age 15-35 - eventual blindness mutation in mitochondrial gene -from mother

Question 44

maternal imprinting

Answer 44

silencing of the maternal allele

Question 45

paternal imprinting

Answer 45

silencing of the paternal allele

Question 46

prader willi

Answer 46

deletion of q12 on chromosome 15 paternal allele short, hypotonia, hyperphagia, obesity, small hands and feet, hypogonadism

Question 47

angelman syndrome

Answer 47

deletion of q12 on chromosome 15 of maternal allele retarded, ataxic gait, seizures, inappropriate laughter -happy puppets

Question 48

gonadal mosaicism

Answer 48

results from mutations that affect cells that form gonads | -offspring manifest the disease

Question 49

indications for genetic analysis in mothers

Answer 49

``` over age 35 previous problems ultrasound deformities abnormal triple test (AFP, betaHCG, estriol) carrier of X-linked disease ```

Question 50

indications for postnatal genetic analysis

Answer 50

congenital anomalies mental retardation unexplained suspected chromosomal abnormalities

Question 51

analysis of acquired genetic alterations

Answer 51

Dx and management of malignancy and infectious disease

Question 52

direct recombinant DNA

Answer 52

sequence gene

Question 53

indirect recombinant DNA

Answer 53

association with markers

Question 54

SNP

Answer 54

single nucleotide polymorphism

Question 55

repeat length polymorphisms

Answer 55

microsatellites - 2-6 bp, 1 kb length | minisatellite - 15-70 bp, 1-3kb length

Question 56

epigenetic alterations

Answer 56

heritable genetic changes without change in DNA sequence

Question 57

RNA analysis

Answer 57

for RNA virus | chromosomal translocation analysis