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Flashcards in Cystic fibrosis Deck (35)
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1
Q

CF carrier frequency?

A

1/25

2
Q

CF incidence?

A

1 in 2500 live births

3
Q

Where is CFTR and what size?

A

7q31.2, 27 exons

4
Q

What cells are affected in classical CF?

A

Mucus-producing cells in exocrine glands

5
Q

Organs which are affected?

A

Lungs and respiratory tract, pancreas, gut, male genital tract

6
Q

Condition which occurs in 10-20% of newborns with known CF?

A

Meconium ileus- failure to pass meconium due to “blocked” intestine

7
Q

Diagnostic requirements for CF?

A

One or more phenotypic feature + either 2 known disease causing mutations, or 2x sweat test with Cl greater than 60

8
Q

Main cause of morbidity and mortality?

A

Pulmonary disease

9
Q

Mean survival?

A

40 years (56 years if pancreatic function intact)

10
Q

Genotype phenotype correlation:

a) pancreatic sufficiency
b) pulmonary disease
b) male infertility

A

a) good
b) poor
c) good

11
Q

Strcture and function of CFTR protein?

A

Three domain intramembrane protein which regulates movement of Cl ions

12
Q

Commonest mutation in:

a) white UK
b) Ashkenazi jews

A

a) F508

b) W1282X (nonsense)

13
Q

Majority of CF mutations are what type?

A

Single nucleotide changes

14
Q

Classes of CF mutation? (1-5)

A

1- affects translation (G542X)
2- affects protein maturation (F508del)
3- affects function of protein at cell surface
4- causes a decrease in Cl conductance (R1347P)
5- cause decrease in synthesis of CFTR

15
Q

Mutation classes associated with a) classical phenotype b) milder phenotype

A

a) 1, 2, some 3

b) 4, 5, some 3

16
Q

Why are CF mutations common? (2)

A
Founder effect- loss of genetiuc variation that occurs when a new population is established by a small number of individuals from a larger population
Heterozygote advantage- when the heterozygote has a greater relative fitness than either class of homozygote
17
Q

CF-related disease which may be seen in men with CF, and in those who have mutations in CFTR gene but don’t present as classical CF

A

Congenital bilateral absence of the vas deferens (CBAVD)

18
Q

Partially-functioning allelels associated with CBAVD?

A

R117H or 5T

19
Q

What should be checked when “obstructive azoospermia” is written on the reqest form, or when R117H has been identified?

A

poly T status

20
Q

What affects the efficiency of splicing adjacent to the exon 9 acceptor splice site?

A

Tract of thymidine residues which can be 5, 7 or 9 long. 5T is least efficient- reduced production of functional CFTR protein. 9T is the common allele

21
Q

Combinations of thymidine residues and mutations:

a) F508del on one chromosome, R117H in cis with 5T
b) F508del on one chromosome, R117H in cis with 7T
c) 5T on one chromosome, 5T or CF mutation in trans
d) F508 on one chromosome, R117H in cis wit 9T

A

a) classical CF
b) no symptoms or should show CF-related disease
c) benign or could show CF related disease
d) rarely found, benign

22
Q

F508del is usually found in cis with…

A

9T

23
Q

What other site affects splicing efficiency? What is the commonest size of this?

A

Upstream of exon 8 polyT, a TG repeat tract. 11 repeats is normal

24
Q

What is the worst combination involving TG repeats?

A

12 or 13 repeats in cis with FT on one chromosome, severe CF mutation in trans

25
Q

Testing for CF?

A

ARMS

26
Q

Which CF kit can test poly T status?

A

CFEU2 (the other one is CF29)

27
Q

Mutations tested by CF29?

A

29 mutations, uses gel electrophoresis. 90% of European Caucasian mutations

28
Q

Mutations tested by CFEU2?

A

50% mutations and uses capillary electrophoresis

29
Q

What do Tube A and Tube B in CFEU2 contain?

A

Tube A- all mutation specific primers and WT F508. Primers for Poly T
Tube B- all other WT primers- only required to determine zygosity if mutation identified in Tube A and it is not F508

30
Q

Dye coloures in CFEU2:

a) WT
b) mutant
c) hypervariable markers

A

a) green
b) blue
c) red- if these are absent the test has failed, can also use as an identity check

31
Q

How is testing for rare CF mutations carried out?

A

Gene screen by means of sequecning, MLPA or linkage analysis (can put markers around cf gene to identify the high risk haplotype)

32
Q

How could false negatives/heterozygotes being wrongly called as homozygotes result from eithr CF mutation assays?

A

snp under primer binding site

33
Q

Mutation which is more prevalent in Asian populations? What is the issue with testing for this?

A

Y569D. Don’t get ethnicity details on referral cards and using surname is not an accurate method of determining ethnicity

34
Q

What age does an individual need to be in order to be tested for CF?

A

at least 16

35
Q

What is the risk of the asymptomatic sibling of a patient being a carrier?

A

2/3