Ch 5 Genetic Disorders

Question 1

Mendelian Disorders

Answer 1

highly penetrant, mutations in single gene, large effects, follows Mendelian inheritance

Question 2

Chromosomal Disorders

Answer 2

high penetrance, alterations in autosomes or sex chromosomes

Question 3

Complex multigenic disorders

Answer 3

multipe varient forms, varying penetrance, accumulation of several polymorphisms = disease state

Question 4

Conservative missense mutations

Answer 4

have little to no effect on the function of the protein

Question 5

Nonconservative missense mutation

Answer 5

change the function of the protein (ie sickle cell anemia)

Question 6

Mutations within non coding sequences

Answer 6

defective transcription/translation

Question 7

deletions and insertions

Answer 7

frameshift mutation , everything downstream is effected

Question 8

trinucleotide repeat mutations

Answer 8

amplification of a sequence of 3 nucleotides throughout generatons ie Fragile X syndrome

Question 9

almost all inborn error of metabolism are what type of mutation?

Answer 9

autosomal recessive

Question 10

abnormal fibrillin protein d/t mutation in FBN1 on chromosome 15

Answer 10

Marfan syndrome

Question 11

Pt is tall, long extremities, prominent supraorbital ridges, scoliosis, ectopia lentis, mitral valve prolapse

Answer 11

Marfan symdrome

Question 12

deleterious effect on vascular smooth muscle in Marfan syndrome is d/t what?

Answer 12

excessive TGF beta secretion d/t fibrillin deficiency

Question 13

Skin is hyper extensible, extremely stretchable, fragile and vulnerable to trauma. Joints are hypermobile. Connective tissue is fragile.

Answer 13

Ehlers-Danlos Syndrome

Question 14

defective synthesis of structure of fibrillar cartilage

Answer 14

Ehlers-Danlos Syndrome

Question 15

Kyphoscoliosis type of EDS

Answer 15

autosomal recessive, most common

deficient lysyl hydroxylase enzymes which is needed for collagen synthesis

Question 16

Vacular type of EDS

Answer 16

autosomal dominant

abnormalities in type III collagen (blood vessels and viscera)

Question 17

Arthrochalasia type of EDS

Answer 17

autosomal dominant

defect in conversion of type I procollagen to collagen

Question 18

Dermatosparaxis type

Answer 18

autosomal recessive

defect in conversion of type I procollagen to collagen

Question 19

Classic type EDS

Answer 19

mutations in type V collagen

Question 20

mutation in gene for LDL receptor causes

Answer 20

familial hypercholesterolemia

Question 21

elevated plasma cholesterol, premature atherosclerosis, xanthomas, and increased risk of MI

Answer 21

familial hyperhcolesterolemia

Question 22

inability to catabolize GM2 gangliosides d/t mutation in alpha subunit locus on chromosome 15

Answer 22

Tay-Sachs disease

Question 23

severe deficiency of hexoaminidase A

Answer 23

Tay-Sachs disease

Question 24

Pt is of Jewish/Eastern European descent presents with sx at 6mo, motor/mental deterioration, cherry red spot in macula, death by age 2-3 years.

Answer 24

Tay-Sachs disease

Question 25

Where does GM2 gangliosides accumulate?

Answer 25

heart, liver, spleen, CNS/ANS, retina

Question 26

on histology, intracellular inclusions in lysosomes | disease and function?

Answer 26

Tay-Sachs disease | lead to progressive destruction of neurons

Question 27

inherited deficiency in sphingomyelinase (chromosome 11)

Answer 27

Niemman-Pick disease

Question 28

Pt with splenomegaly, gyri are sunken and sulci are wide, pt died at 1-2 years of age. Pt of Jewish descent. Enlarged lysosomes

Answer 28

Neimman Pick disease type A

Question 29

Adult Jewish pt with enlarged lysosomes and accumulation of sphingomyelin in the spleen.

Answer 29

Neimman Pick disease type B

Question 30

mutation in NPC1 leads to defective lipid transport

Answer 30

Neimman Pick disease type C

Question 31

Accumulation of cholesterol and gangliosides.

Answer 31

Neimman Pick disease type C

Question 32

Disease presents in childhood with ataxia, ertical supranuclear gaze palsy, dystonia, dysarthria and psychomotor regression.

Answer 32

Neimman Pick disease type C

Question 33

What is the most common lysosomal storage disorder?

Answer 33

Gaucher disease

Question 34

defective glucocerebrosidase activity

Answer 34

Gaucher disease

Question 35

where does glucocerebroside accumulate in Gaucher disease?

Answer 35

Phagocytes or CNS

Question 36

Gaucher disease type I

Answer 36

mononuclear phagocytes of the body (sk m and spleen) in Jewish population Does not involve brain

Question 37

Gaucher disease type II

Answer 37

``` in infants no glucocerebroside activity not in Jewish affects brain tissue death at early age ```

Question 38

Gaucher disease type III

Answer 38

intermediate between type I and II | systemic and CNS involvement in early adolescents/adulthood

Question 39

Tissue paper cytoplasm

Answer 39

Gaucher disease

Question 40

deficiency in enzymes that metabolize GAGs

Answer 40

Mucopolysaccharidoses

Question 41

Pt with coarse facial features, clouding of the cornea, joint stiffness, and mental retardation

Answer 41

Mucopolysaccharidoses

Question 42

Cell have enlarged balloon appearance

Answer 42

Mucopolysaccharidoses

Question 43

Pt presents with hepatosplenomegaly, skeletal deformities, valvular lesions, and subendothelial artery deposits and brain lesions

Answer 43

Mucopolysaccharidoses

Question 44

deficiency of alpha1-iduronidase | Pt with HSM, coarse facial features, skeletal abnormalities, death around 6-10 yo

Answer 44

Hurler syndrome (MPS1)

Question 45

Hunter Syndrome

Answer 45

MPS II, X linked, milder clincial course, like Hurler sydnrome

Question 46

Pt with hepatomegaly and hypoglycemia

Answer 46

Hepatic glycogen storage disorder (von Gierke diseases/type I)

Question 47

Pt present with muscle cramps after exercise and lactate levels which cannot rise in the blood d/t blocked glycolysis

Answer 47

Myopathic glycogen storage disorder (McArdle disease/ type V)

Question 48

``` death in early life with cardiomegally def in alpha glucosidase or branching enzyme ```

Answer 48

Systemic glycogen storage disorder (Pompe disease/type II)

Question 49

flat facial profile, oblique palpebral fissures, epicanthic folds, severe mental retardation. Heart defects, atresias of esophagus and small bowel, inc risk of leukemia, neuropathic changes

Answer 49

Trisomy 21 (Down Syndrome)

Question 50

Chromosome 22q11.2 deletion

Answer 50

DiGeoge's syndrome

Question 51

congential heart defects, abnormalities of the palate and face, developmental delay, variable degress of T cell immunodeficiency and hypocalcemia

Answer 51

Chormosome 22q11.2 deletion

Question 52

low set ears, short neck, overlapping fingers, congenital heart defects, renal malformation, limited hip abduction, rocker bottom feet, prominent occiput, mental retardation, micrognathia

Answer 52

Trisomy 18 (Edwards syndrome)

Question 53

microphthalmia, polydactyl, cardiac defects, umbilical hernia, rocker bottom feet, renal defects, cleft lip and palate, microcephaly and mental retardation

Answer 53

Trisomy 13 (Patau Syndrome)

Question 54

elongated body, small atrophic testes, small penis, lack of secondary male sex characteristics, gynecomastia, infertility

Answer 54

Klinefelter Syndrome (XXY)

Question 55

Klinefelter Syndrome is due to what

Answer 55

nondisjunction 2 more X and 1 or more Y

Question 56

lymphedema, neck webbing, cardiac abnormalities, failure to develop secondary sex characteristics, short stature, and amenorrhea. Streak ovaries.

Answer 56

Turner Syndrome (X)

Question 57

second most common cause of genetic mental retardation

Answer 57

Fragile X syndrome

Question 58

mutation in FMR1 gene causes absence o the FMRP protein in brain and testes

Answer 58

Fragile X sydnrome

Question 59

mental retardation, long face with large mandible, large everted ears, large testicles (macro-orchism), hyperextensible joints, arched plate, and mitral valve prolapse

Answer 59

Fragile X syndrome

Question 60

progressive loss of central vision and eventually complete blindness disease/d/t what?

Answer 60

Leber Hereditary Optic neuropathy mutation in mitochondrial genes from mother

Question 61

deletion of paternal chromosome 15

Answer 61

Prader Willi Syndrome

Question 62

mental retardation, short stature, profound hyperphagia, obesity, small hands, and hypogonadism

Answer 62

Prader Willi Syndrome

Question 63

deleton on maternal chormosome 15

Answer 63

Angelman Syndrome

Question 64

mental retardatoin, ataxic gait, seizures and inappropriate laughter (happy puppet)

Answer 64

Angelman Syndrome