Genetics

Question 1

Which type of Ehlers-Danlos syndrome is most popular?What is the mode of inheritance?
What is the mechanism of the defect?
What are the typical clinical features?

Answer 1

Type 4: Kyphoscoliosis
Autosomal recessive
Defect in lysyl hydroxylase causes decreased hydroxylation of lysine residues during collagen synthesis.
Joint laxity, congenital scoliosis, hypotonia, and ocular fragility

Question 2

What is Ehlers-Danlos Syndrome?

Answer 2

Genetic disorder causing some defect in fibrillar collagen synthesis/ structure
Involves tissues rich in collagen (skin, ligaments, joints)

Question 3

What is Marfan Syndrome?

Answer 3

Inherited defect in fibrillin-1 causing abnormalities in tissues requiring elastin

Question 4

What are the clinical manifestations of Marfan Syndrome

Answer 4

Loss of structural support in microfibril rich connective tissues
Excessive activation of TGF-B signaling
Mitral valve lesions
Aortic lesions
Lens dislocations
Unusually tall with long digits

Question 5

what chromosome does the defect occur for Marfan Syndrome?

Answer 5

chromosome 15

Question 6

Which lysosome storage disorders target Ashkenzaic Jews?

Answer 6

Tay-Sachs

Neimann-Pick

Question 7

Most common lysosomal storage disorder

Answer 7

Gaucher Disease

Question 8

Defect in Hexosaminidase A

Answer 8

Tay-Sachs

Question 9

what chormosome is associated with Tay-Sach Disease

Answer 9

Chromosome 15

Question 10

Life expectancy of Tay-Sachs patient

Answer 10

<3 years

Question 11

Morphology characteristic of Neimann-Pick

Answer 11

foamy macrophages

Question 12

What chromosome is associated with Neimann-Pick

Answer 12

chromosome 11

Question 13

what protein is deficient in Neimann-Pick

Answer 13

Sphingomyelinase

Question 14

Differences between types of Neimann-Pick

Answer 14

Infantile: includes neurologic involvement, life expectancy ~3 years
Adult: only organomegaly and usually survive into adulthood

Question 15

What protein is mutated in Gaucher Disease?

Answer 15

Glucocerebrosidase

Question 16

Signs of Gaucher Disease

Answer 16

splenomegaly
expansion of bone marrow space
CNS involvement

Question 17

47 XXY or 48XXXY

Answer 17

Kleinfelter Syndrome

Question 18

Associations of Kleinfelter Syndrome

Answer 18

mitral valve prolapse
osteoporosis
breast cancer
extragonadal tumors
SLE

Question 19

Clinical manifestations of Kleinfelter Syndrome

Answer 19

tall
gynecomastia
poor muscle tone
reduced testosterone but high FSH
lower IQ than siblings

Question 20

Mechanism of Fragile X Syndrome

Answer 20

long repeating sequences of 3 nucleotides caused by mutation of FMR1 gene
The more the repeats exceed 230, the more the chromosome becomes abnormally methylated, promoting transcrptional suppression of FMR-1
Abscence of FMRP leads to phenotypic changes

Question 21

Highest cause of mental retardation

Answer 21

Down Syndrome

Question 22

second highest cause of mental retardation

Answer 22

Fragile X syndrome

Question 23

which chromosome is involved in Angelmann and Prader-Willi syndrome

Answer 23

15q12

Question 24

which gene is active in Angelmann syndrome

Answer 24

Prader willi

Question 25

which gene is imprinted in Prader willi syndrome

Answer 25

prader willi

Question 26

what is genetic imprinting

Answer 26

normal selective inactivation of maternal or paternal alleles, usually via methylation or deacetylation

Question 27

Deletion of maternal 15q12

Answer 27

Angelmann Syndrome

Question 28

Deletion of Paternal 15q12

Answer 28

Prader-Willi Syndrome

Question 29

physical features of prader willi

Answer 29

``` short stature mental retardation hypotonia hyperphagia hypogonadism small hands/ feet ```

Question 30

physical features of Angelmann syndrome

Answer 30

ataxic gait seizure= inappropriate laughter mental retardation

Question 31

What protein is defective in Classic Galactosemia

Answer 31

Gal-1-Phosphate Uridyl Transferase

Question 32

What is Cystic Fibrosis

Answer 32

defective CF gene causes malfunction of exocrine glands, leading to increased mucous viscosity and chronic pulmonary disease

Question 33

what ion is increased in the secretions of CF patients

Answer 33

Chloride

Question 34

Most common clinically encountered inborn error of amino acids

Answer 34

PKU

Question 35

what enzyme is defective in PKU?

Answer 35

Phenylalanine hydroxylase

Question 36

characteristics of PKU

Answer 36

decreased pigmentation musty body odor microcephaly mental deterioration

Question 37

What else could cause PKU?

Answer 37

deficiencies in enzymes needed to produce BH4 or BH2 reductase

Question 38

What causes Maple Syrup Urine Disease

Answer 38

defects in proteins composing branched chain alpha ketoacid dehydrogenase complex

Question 39

characteristics of MSUD

Answer 39

``` maple syrup odor to urine high urinary levels of ketoacids, isoleucine and valine mental/ physical disability feeding problems neonatal death ```

Question 40

What causes albinism

Answer 40

defective tyrosine metabolism to DOPA

Question 41

What enzyme is defective in homocystinuria?

Answer 41

Cystathionine Beta synthase

Question 42

what cofactor is needed to produce cystathionine

Answer 42

PLP (B6)

Question 43

characteristics of homocystinuria

Answer 43

lens dislocation increased risk of thrombi high serum and urine homocysteine intellectual disability

Question 44

What accumulates in Alkaptonuria

Answer 44

homogentisic acid

Question 45

What causes Alkaptonuria

Answer 45

incomplete metabolism of Phenylalanine and Tyrosine due to homogentisic oxidase

Question 46

characteristics of Alkaptonuria

Answer 46

dark urine on standing defective cardiac valves dark pigmentation od fibrous tissues and cartilage