Autosomal Recessive Disorders Flashcards Preview

M2M Unit II > Autosomal Recessive Disorders > Flashcards

Flashcards in Autosomal Recessive Disorders Deck (66):
1

Compound heterozygote

one who carries two different mutant alleles of the same gene.

1

Individuals with the Z/Z genotype have only ____ α1-AT activity and account for most cases of the disease.

10-15% of normal

1

ATD treatment?

delivering human SERPINA1 to the pulmonary epithelium

2

Most PKU cases are caused by defects in the _____ encoding phenylalanine hydroxylase.

PAH gene

3

ATD carrier frequency?

~1/25

3

____, relevant to ATD, is made in the liver and secreted into plasma.

α1-antitrypsin (ATT or SERPINA1)

3

The β subunit gene HEXB resides on chromosome ___.

5

4

Most PKU patients are ____ (i.e. having two different mutant alleles of the PAH gene).

compound heterozygotes

4

ATD

α1-Antitrypsin Deficiency

5

What is the frequency of T-S in the general population?

1/360,000

6

HexA is a heterodimer of ___, which are encoded by the HEXA and HEXB genes, respectively.

αβ

7

Phenylketonuria (PKU) phenotype

Microcephaly; possible profound mental retardation;. seizures, tremors, and gait disorders

7

Most ATD diseases are associated with two mutant alleles, the ___ and ___ alleles.

Z and S

8

findings in PKU: urine and sweat

High levels of phenylalanine metabolites and "mousy" odor

8

Elastase can destroy the connective tissue proteins (particularly elastin) of the lung, causing _____ and ______.

alveolar wall damage; emphysema

9

Other high-risk groups for T-S are ____, _____, and _____.

certain French-Canadian communities of Quebec, the Old Order Amish community in Pennsylvania, and the Cajun population of Louisiana

11

What does T-S disease destroy?

neurons in the brain and spinal cord

11

Although HexA is a ubiquitous enzyme, the impact of T-S is primarily in the ____ where most of GM2 ganglioside is synthesized.

brain

12

Allelic heterogeneity

the existence of multiple mutant alleles of a single gene

13

PKU carrier frequency

1/50

13

α1-antitrypsin (ATT or SERPINA1) is made in the ____ and secreted into ____.

liver; plasma

15

plasma findings in PKU

High phenylalanine and low tyrosine levels

15

What is the frequency of T-S in the Ashkenazic Jewish population?

1/3600

16

_____ patients have defects in both Hexosaminidase A and Hexosaminidase B (HexB).

Sandhoff disease

18

Sandhoff disease is caused by a defective ___ subunit; both ____ and ____ activities are affected.

β; HexA and HexB

19

Although HexA is a ubiquitous enzyme, the impact of T-S is primarily in the brain where most of _____ is synthesized.

GM2 ganglioside

20

high-risk group

a population with higher-than-expected risk for a particular AR disease

20

_____ can destroy the connective tissue proteins (particularly elastin) of the lung, causing alveolar wall damage and emphysema.

Elastase

21

Elastase can destroy the ______ , causing alveolar wall damage and emphysema

connective tissue proteins (particularly elastin) of the lung

23

T-S

Tay-Sachs disease (GM2 gangliosidosis type I)

23

Inability to degrade ______ results in up to 300-fold accumulation of this sphingolipid inside swollen lysosomes in neurons of the central nervous system.

GM2 ganglioside

25

ATD disease frequency?

1/2,500

26

The main target of _____ is elastase.

SERPINA1

28

What is the cofactor of PAH?

BH4

29

Elastase is released by _____ in the lung.

neutrophils

30

ATD patients have a 20-fold increased risk of developing _____.

emphysema

30

Defective _____ needed for metabolizing GM2 is responsible for T-S.

hexosaminidase A (HexA)

31

Z/S compound heterozygotes have ____ α1-AT activity and may develop emphysema.

30-35 % of normal

33

frequency of PKU

1/10,000 births

34

______ is released by neutrophils in the lung.

Elastase

36

_____ presents the same neurological symptoms as T-S.

Sandhoff disease (GM2 gangliosidosis type II)

37

An eye abnormality called ____ is a characteristic of T-S

“cherry-red spot"

39

The ____ in PKU damages the developing central nervous system in early childhood and interferes with the function of the mature brain

high phenylalanine level

41

Individuals with ___ genotype have 50-60% of normal α1-AT activity and usually do not express disease symptoms.

S/S

41

The most common mutant allele in T-S is _____.

a 4 bp insertion in exon 11 of HEXA

42

Parental consanguinity

parents sharing one or more common ancestors.

43

The α subunit gene HEXA resides on chromosome ___.

15

44

In ATD, the ___ allele (Glu264Val) expresses an unstable protein that is less effective.

S

45

The PAH gene encodes phenylalanine hydroxylase, a liver enzyme that catalyzes the conversion of ____ using molecular oxygen and a cofactor tetrahydrobiopterin (BH4).

Phe to Tyr

46

In ATD, the ___ allele (Glu342Lys) encodes a misfolded protein that aggregates in the endoplasmic reticulum (ER) of liver cells, causing damage to the liver in addition to the lung.

Z

47

The SERPINA1 gene is on chromosome ___.

14

49

HexA and HexB refer to the two _____; HEXA and HEXB refer to two ____.

enzymes; genes

50

___ compound heterozygotes have 30-35 % of normal α1-AT activity and may develop emphysema.

Z/S

52

Why does smoking accelerate the onset of emphysema in ATD pts?

Tobacco smoke damages the lung-- more neutrophils to the lung for protection-- More neutrophils release more elastase-- more severe lung damage

54

Individuals with S/S genotype have ____ α1-AT activity and usually do not express disease symptoms.

50-60% of normal

55

T-S is caused by a defective ___ subunit; only ___ activity is affected.

α; HexA

56

The main target of SERPINA1 is _____.

elastase

57

Which chromosome is the PAH gene located at?

12

58

Many ATD patients also develop ____ and have an increased risk of ____ due to the accumulation of a misfolded α1-AT mutant protein in the liver.

liver cirrhosis; carcinoma

59

Individuals with the ___ genotype have only 10-15% of normal α1-AT activity and account for most cases of the disease.

Z/Z

60

What screening test is used for ATD?

Sequence specific oligonucleotide probes

62

The PAH gene encodes ____, a liver enzyme that catalyzes the conversion of Phe to Tyr using molecular oxygen and a cofactor tetrahydrobiopterin (BH4).

phenylalanine hydroxylase

63

Defective hexosaminidase A (HexA) needed for metabolizing ___ is responsible for T-S.

GM2

64

PKU treatments?

1) low-phenylalanine diet 2) oral BH4, supplements

65

Inability to degrade GM2 ganglioside results in up to 300-fold accumulation of this sphingolipid inside swollen _____ in neurons of the central nervous system.

lysosomes

66

Hex B is a homodimer of ____.

ββ