Autosomal Recessive

Question 1

A diseases know as STUPID1 is a defect in the protein known as SMRT1. There are many different alleles that affect the SMRT1 gene. Three such are A+, A, and A-, where A+ is the wild type allele. How would you classify someone with the genotype A+,A+?

Answer 1

Homozygous

Question 2

A diseases know as STUPID1 is a defect in the protein known as SMRT1. There are many different alleles that affect the SMRT1 gene. Three such are A+, A, and A-, where A+ is the wild type allele. How would you classify someone with the genotype A+,A?

Answer 2

Simple Heterozygote

Question 3

A diseases know as STUPID1 is a defect in the protein known as SMRT1. There are many different alleles that affect the SMRT1 gene. Three such are A+, A, and A-, where A+ is the wild type allele. How would you classify someone with the genotype A-,A?

Answer 3

Compound heterozygote

Question 4

A diseases know as STUPID1 is a defect in the protein known as SMRT1. There are many different alleles that affect the SMRT1 gene. Three such are A+, A, and A-, where A+ is the wild type allele. These three alleles demonstrate the concept of_______________

Answer 4

Allelic Heterogeneity

Question 5

What are the phenotypes of PKU?

Answer 5

Its a High disorder:

1. High phenylalanine in blood
2. High phenylalanine metabolits in urine
3. HYPERactivity and epilepsy
4. Mind high in the clouds (mental retardation and microcephaly)

False negatives if tested within 24hrs of life b/c of maternal phenylalanine.

Question 6

What is the biochemical cause of PKU?

Answer 6

98%-Caused by a mutation in the Phenylalanine Hydroxylase (PAH) enzyme. PAH converts phenylalanine into Tyrosine.

2% caused by defects in BH4 cofactor

Question 7

When using mass spec to test for PKU in an infant, when should test(s) be ordered?

Answer 7

Baseline test at birth (before ingesting any food), then 2-3 days later.

Look for elevated F and/or low Y in blood.

Question 8

Describe the mechanism of ATD

Answer 8

α1-antitrypsin is a protease inhibitor that normally inhibits Elastase. Caused by defects in α1-AT (SERPINA1) gene.

In lungs, dec α1-antitrypsin–> Ž uninhibited elastase
in alveoli Ž–> elastic tissue breakdown –>Ž
emphysema.

Question 9

A patient affected with ATD comes to your clinic and shows signs of emphysema but no signs of liver disease. Which allele do you suspect your patient has? What are the characteristics of the two alleles?

Answer 9

S allele, which makes unstable SERPINA1 protein.
50-60% of normal SERPINA1

Z allele- Most common
15% of normal SERPINA1
Protein misfolding. Accumulates in liver–> liver damage

Question 10

Describe Tay-Sach disease:

Answer 10

Lysosomal storage disorder that destroys CNS. Prominent in Jews.

Symptoms begin around 3-6mo and babies usually die around 2-4yrs.

• Muscle weakness and startling are early signs.
• Progressive loss of brain functioning.

Question 11

What are the biochemical effects of T-S disease?

Answer 11

Accumulation of Gm2 Ganglioside, a normal component of neural cell membranes.

Defect in Hexosaminidase alpha subunit (HEXA)

Question 12

What is a HEXB mutation associated with?

Answer 12

Sandhoffs disease

Question 13

Which is more severe, the B Variant of Tay-Sachs or the AB variant?

Answer 13

AB

Question 14

True or False:

The AB variant of Tay-sachs is caused by mutations in both the Alpha and Beta subunits of HEX.

Answer 14

FALSE:

Its cause by a mutation in GM2AP