Cystic Fibrosis

Question 1

Which one of following defects causes multisystem symptoms in patients with CF?
A.Transmembrane sodium channel
B.Transmembrane chloride channel
C.Transmembrane cation channel
D.Transmembrane calcium channel
E.Transmembrane ion channel

Answer 1

B.Transmembrane chloride channel

Question 2

Which one of the following describes the functional changes of the mutations in CF?
A.Dominant negative
B.Gain of function
C.Loss of function
D.Not sure
E.None of the above

Answer 2

C.Loss of function

Question 3

How frequently do patients with congenital bilateral absence of the vas deferens (CBAVD) have at least one variant in the CFTR gene including the 5T variant?
A.20%
B.35%
C.50%
D.75%
E.95%

Answer 3

D.75%

Question 4

How frequently do patients with congenital bilateral absence of the vas deferens (CBAVD) have two variants in the CFTR gene including the 5T variant?
A.20%
B.35%
C.50%
D.75%
E.95%

Answer 4

C.50%

Question 5

How many mutations/variants are in the updated minimum mutation panel recommended by ACMG in 2004 for CF (not counting the reflex test)?
A.15
B.23
C.25
D.60
E.139

Answer 5

B.23

1500 mutations have been described in CFTR
2004, the panel was reduced to 23 mutations by the removal of 1078delT and I148T. The current panel of 23 mutations recommended by the ACMG, represents only 1.2% of all mutations (over 1800 in total) reported in the CFTR gene, but accounts for approximately 85% of mutations occurring in CF patients and covers both affected alleles in 72% of patients.

Question 6

What is the carrier frequency of cystic fibrosis (CF) in Ashkenazi Jews?
A.1/16
B.1/24
C.1/33
D.1/58
E.1/61
F.1/94

Answer 6

B.1/24
detection rate of the ACMG-recommended 23 mutations is 94%

Question 7

What is the carrier frequency of cystic fibrosis (CF) in Caucasians?
A.1/17
B.1/25
C.1/33
D.1/42
E.1/60
F.1/94

Answer 7

B.1/25
detection rate of the ACMG 23 mutations is 88%

Question 8

Which one of the populations below has the lowest cystic fibrosis carrier frequency?
A.Ashkenazi Jewish
B.European Caucasian
C.Hispanic American
D.African American
E.Asian American
F.None of the above

Answer 8

E.Asian American

Question 9

Which individual below has the lowest risk of being a cystic fibrosis (CF) carrier, assuming that she/he does NOT have a family history of CF and is apparently healthy?
A.Descendant of AJ/European
B.Descendant of European Caucasian/Hispanic Americans
C.Descendant of African American/Hispanic Americans
D.Descendant of African American/Asian Americans
E.Descendant of Hispanic American/Asian Americans
F.None of the above

Answer 9

D.Descendant of African American/Asian Americans

Question 10

Which of the following orders is the correct one for cystic fibrosis carrier frequency (from highest to the lowest)?
A.Ashkenazi Jewish>European Caucasian>Hispanic American>African American> Asian American
B.Ashkenazi Jewish>European Caucasian>African American>Hispanic American> Asian American
C.Ashkenazi Jewish>European Caucasian>African American>Asian American> Hispanic American
D.Ashkenazi Jewish>European Caucasian>Hispanic American>Asian American> African American
E.Ashkenazi Jewish>European Caucasian>Asian American>African American> Hispanic American
F.None of the above

Answer 10

A.Ashkenazi Jewish>European Caucasian>Hispanic American>African American> Asian American

Question 11

Which one of the following is the approximate analytical sensitivity of the ACMG-recommended cystic fibrosis (CF) carrier test panel with 23 mutations in Ashkenazi Jews?
A. 95%
B. 90%
C. 80%
D. 70%
E. 60%

Answer 11

A. 95%

Question 12

Which one of the following is the approximate analytical sensitivity of the ACMG-recommended cystic fibrosis (CF) carrier test panel with 23 mutations in non-Hispanic Caucasians?
A. 95%
B. 90%
C. 80%
D. 70%
E. 60%

Answer 12

B. 90%

Question 13

The mutation that needs to be detected is ATTTGGTTCTCACCTGA[a/g]CAGCGGCTCACAGTTGATGA. Which pair of probes would she pick as the probes for this mutation?
A. TGGTTCTCACCTGAaCAGCGGCTCACAGTT and TGGTTCTCACCTGAgCAGCGGCTCACAGTT
B. AACTGTGAGCCGCTGtTCAGGTGAGAACCA and TGGTTCTCACCTGAgCAGCGGCTCACAGTT
C. TGGTTCTCACCTGAtCAGCGGCTCACAGTT and AACTGTGAGCCGCTGcTCAGGTGAGAACCA
D. AACTGTGAGCCGCTGaTCAGGTGAGAACCA and AACTGTGAGCCGCTGcTCAGGTGAGAACCA

Answer 13

A. TGGTTCTCACCTGAaCAGCGGCTCACAGTT and TGGTTCTCACCTGAgCAGCGGCTCACAGTT

Question 14

Which one of the following assays has better analytical sensitivity than the others to detect patients with cystic fibrosis (CF)?
A. ACMG-recommended 23-mutation panel B.CFTR gene Sanger sequencing
C. Immunoreactive trypsinogen (IRT)-IRT
D. Sweat chloride test E.None of the above

Answer 14

C. Immunoreactive trypsinogen (IRT)-IRT

immunoreactive trypsinogen (IRT) screening test for cystic fibrosis (CF) has a high sensitivity but is not very specific, resulting in a large number of screened positive infants found to have a normal sweat test (low positive predictive value, high false positive rate).

Question 15

European preconception counseling. Husband with CF brother. Wife unremarkable. What is the risk that the couple’s firstborn child will have CF?
A.1/54
B.1/150
C.1/200
D.3/400
E.None of the above

Answer 15

B.1/150

husband 2/3 chance of being a carrier

(2/3)*((1/25) x (1/4) = 1/150

Question 16

AJ preconception counseling. Wife with CF brother. Husband unremarkable. What is the risk that the couple’s firstborn child will have CF?
A.1/54
B.1/150
C.1/200
D.3/400
E.None of the above

Answer 16

B.1/150

(2/3)*((1/24) x (1/4) = 1/150

Question 17

European prenatal counseling. Wife with CF brother and a carrier. Husband unremarkable. What is the risk that the couple’s firstborn child will have CF?
A.1/25
B.1/50
C.1/100
D.1/200
E.None of the above

Answer 17

C.1/100

1*(1/25) x (1/4) = 1/150

Question 18

AJ wife and Hispanic husband prenatal counseling. CF panel negative in wife. Husband panel pending. What was the wife’s residual risk to be a CF carrier?
A.1/24
B.1/192
C.1/384
D.1/768
E.1/1534
F.None of the above

Answer 18

**D.1/768
Husband is carrier
Prior 1/24
Conditional (1-94%) = 6/100/ 3/50
Joint probability (1/24)((3/50) = 3/1200

Husband is not a carrier
Prior 1- (1/24) = 23/24
Conditional 1
Joint = (23/24)* 1 = 1150/1200

Posterior probability
3/1200/(3/1200+1150/1200) ~400

Question 19

European prenatal counseling. Wife with CF brother. Husband unremarkable. Two healthy children. What is the risk that the couple’s third born child will have CF?
A.1/100
B.1/385
C.1/770
D.1/1540
E.1/3080
F.None of the above

Answer 19

D.1/1540

Husband is carrier
Prior 1/25
Conditional (1/4)^2 = 1/16
Joint probability (1/25)*(1/16) = 1/400

Husband is not a carrier
Prior 1- (1/25) = 24/25
Conditional 1
Joint = (24/25)* 1 = 384/400

Posterior probability
1/400/(1/400+384/400) ~400
1/400 x1 x1/4 = 1/1540

Question 20

Which one of the following methods has been widely used as the first-tier cystic fibrosis (CF) test in newborn screening (NBS) programs in the United States?
A.CFTR gene Sanger sequencing
B.High-performance liquid chromatography (HPLC)
C.Immunoreactive trypsinogen (IRT)
D.Mass spectrometry (MS)
E.Sweat sodium chloride test
F.None of the above

Answer 20

C.Immunoreactive trypsinogen (IRT)

90-95% sensitivity with initial a+/- 2wk repeat

Question 21

The newborn screening (NBS) test for cystic fibrosis (CF) was positive. And Johnny had meconium ileus. Which one of the following findings may lead to the positive NBS CF report?
A.High value of immunoreactive trypsinogen (IRT)
B.Low value of immunoreactive trypsinogen (IRT)
C.High value of sweat chloride
D.Low value of sweat chloride
E.None of the above

Answer 21

A.High value of immunoreactive trypsinogen (IRT)

Question 22

A newborn boy, Johnny, with a p.F508del variant to a Cystic Fibrosis (CF) Foundation–accredited care center for further evaluation and diagnostic testing. Which one of the following assays would be the most appropriate to confirm the diagnosis in Johnny after the positive CF screening?
A.CFTR gene Sanger sequencing
B.High-performance liquid chromatography (HPLC)
C.Immunoreactive trypsinogen (IRT)
D.Mass spectrometry (MS)
E.Sweat sodium chloride test
F.None of the above

Answer 22

E.Sweat sodium chloride test

Question 23

The newborn screening test (NBS) showed elevated immunoreactive trypsinogen (IRT), and a p.F508del mutation was found with the DNA test. Follow-up sweat chloride testing showed a level of 22mmol/L at 16 days of age. Which one of the following would be the most appropriate interpretation of the sweat chloride test results?
A.Normal
B.Intermediate
C.Abnormal
D.Not sure
E.None of the above

Answer 23

A.Normal

infants < 6 months <29 mmol/L
intermediate 30-59 mmol/L
60 or > indicative of CF

Question 24

The newborn screening test (NBS) showed elevated immunoreactive trypsinogen (IRT), and a p.F508del mutation was found with the DNA test. Follow-up sweat chloride testing showed 45mmol/L at 16 days of age. Which one of the following would be the most appropriate interpretation of the sweat chloride test results?
A.Normal
B.Intermediate
C.Abnormal
D.Not sure
E.None of the above

Answer 24

B.Intermediate

infants < 6 months <29 mmol/L
intermediate 30-59 mmol/L
60 or > indicative of CF

Question 25

The newborn screening test (NBS) showed elevated immunoreactive trypsinogen (IRT), and a p.F508del mutation was found with the DNA test. Follow-up sweat chloride testing showed 62 mmol/L at 16 days of age. Which one of the following would be the most appropriate interpretation of the sweat chloride test results? A. Normal B. Intermediate C. Abnormal D. Not sure E. None of the above

Answer 25

C. Abnormal infants < 6 months <29 mmol/L intermediate 30-59 mmol/L 60 or > indicative of CF

Question 26

Which one of the following mutations in the CFTR gene is the most common for cystic fibrosis (CF) worldwide? A. p.F508del B. p.R117H C. p.G551D D. c.1210-12T[5] E. p.G542X

Answer 26

A. p.F508del 70% of CF worlwide

Question 27

Which one of the following mutations is NOT included in the revised American College of Medical Genetics and Genomics (ACMG) cystic fibrosis (CF) carrier screening panel published in 2004, but is in the recommended reflex test? A. p.F508del B. p.R117H C. p.G551D D. c.1210-12T[5] E. 5T/7T/9T

Answer 27

E. 5T/7T/9T -- poly T tracts splice acceptor regions in intron 8 7T/9T polymorphic upstream 2001-->2004, the panel was reduced to 23 mutations by the removal of 1078delT and I148T.

Question 28

Prenatal counseling with wife a carrier of R117H. Husband African American. Which one of the following mutations/variants should also be tested for the wife to interpret this molecular result according to the ACMG recommendation? A. 5T/7T/9T B. TH11/TG12/TG13 C. I507V D. F508C E. None of the above

Answer 28

A. 5T/7T/9T 5T variably penetrant polyT tract in intron 8 causes aberrant exon 9 splicing, variant in the CFTR gene, can be pathogenic in trans while not typically considered a disease-causing mutation on its own, can be associated with cystic fibrosis (CF) when present in combination with other CFTR mutations, particularly the R117H variant -- **R117H pathogenic in cis in CF

Question 29

The results showed that the Caucasian wife was compound heterozygous for R117H and 7T in intron 8. The husband’s test detected a heterozygous p.F508del mutation. What was the risk that their third born child would have CF? A. 1/4 B. 1/16 C. 1/482 D. 1/964 E. 1/1928 F. Not clear G. None of the above

Answer 29

***D. 1/964 Wife is carrier Prior 1/25 Conditional (100%-88% after test) = 1/10 Joint probability (1/25)*(1/10) = 1/250 Wife is not a carrier Prior 1- (1/25) = 24/25 Conditional 1 Joint = (24/25)* 1 = 240/250 Posterior probability 1/250/(1/250+240/250) ~1/241 1/241 x 1 x 1/4 = 1/964

Question 30

The results showed that the wife was compound heterozygous for R117H and 5T in intron 8. Subsequently, the husband’s test detected a heterozygous p.F508del mutation. What was the risk that their firstborn child would have CF? A. 1/4 B. 1/16 C. 1/482 D. 1/964 E. 1/1928 F. Not clear G. None of the above

Answer 30

***F. Not clear

Question 31

The R117H mutation in CFTR is modified by the 5T/7T/9T polymorphism in intron 8. Which one of the following mechanisms explains how 5T/7T/9T modifies phenotypes in patients with R117H? A. The polymorphism affects splicing function. B. The polymorphism affects the modification of mRNA with the polyadenylation at the 3′ end. C. The polymorphism affects the promoter function at the 5′ end. D. The polymorphism affects the enhancer function. E. The polymorphism maps to a locus other than CFTR. F. Unclear. G. None of the above.

Answer 31

A. The polymorphism affects splicing function.

Question 32

Preconception caucasian counseling. Wife tested positive for the F508del mutation. Subsequently, the husband’s test results indicated that he was a carrier of the R117H mutation, and the reflex test found 5T. For which one of the following medical problems would the husband be at risk? A. Heart failure B. Infertility C. Obesity D. Sudden death E. All of the above F. None of the above

Answer 32

B. Infertility R117/5Tclinical presentations from congenital bilateral absence of the vas deferens (CBAVD) to classic CF. R117H/7T is associated with milder forms of CF such as CBAVD

Question 33

The results showed that the wife was a carrier of the R117H mutation, and the reflex test detected 5T. The husband’s test detected a heterozygous p.F508del mutation. Which one of the following statements is the most appropriate one? A. The wife is a CF patient with mild symptoms. B. The wife is not a CF carrier. C. The fetus will have 25% chance of having CF. D. Not sure. E. None of the above.

Answer 33

D. Not sure. about 5% of the US population has the 5T polymorphism. If positive for 5T, the laboratory will request peripheral-blood specimens from the parents to determine whether the 5T polymorphism is in cis or trans with the R117H allele in order to provide additional information for genetic counseling.

Question 34

The results showed that the wife was a carrier of the R117H mutation, and the reflex test detected 5T. Subsequently, the husband’s test results turned out to be negative. Which one of the following statements is appropriate? A. The child is not at risk for CF. B. The child still has significant risk for CF. C. The child is at risk for infertility if it is a male. D. All of the above. E. None of the above.

Answer 34

C. The child is at risk for infertility if it is a male. And among CBAVD patients, 78% had at least one CFTR mutation and 46% had two.

Question 35

The results showed that the Caucasian wife was a carrier of the R117H mutation, and the reflex test detected 7T. The husband’s test results turned out to be negative. What was the residual risk that their firstborn child would have CF? A. 1/4 B. 1/50 C. 1/964 D. >1/3856 E. None of the above

Answer 35

D. >1/3856 Compound heterozygous R117 and 7T are considered benign Wife is a carrier Prior 1/25 Conditional (1-90%) = 1/10 Joint probability (1/25)*((1/10) = 1/250 Wife is not a carrier Prior 1- (1/25) = 24/25 Conditional 1 Joint = (24/25)* 1 = 240/250 Posterior probability 1/240/(1/240+230/240) 241 1/241 x1/241 x1/4 = 1/232,324

Question 36

Healthy Caucasian prenatal testing. The results showed that the wife was a carrier of the R117H mutation and 5T. Which one of the following would be the most appropriate next step in the workup? A. Test the husband with the same CF mutation panel. B. State in the report that the wife is not a carrier. C. Recommend prenatal CF diagnostic testing to the couple. D. Recommend CF testing to the wife’s parents and/or other family members. E. The posttest risk is significantly decreased. There is no need for follow-up.

Answer 36

A. Test the husband with the same CF mutation panel. The 5T variant paired (in trans) with a CF mutation has been found in men with CBAVD. And R117H mutation can also cause classic CF when in cis with 5T

Question 37

Caucasian prenatal testing. The results showed that the wife was a carrier of the R117H mutation and 5T. The husband’s test detected a heterozygous p.F508del mutation. Which one of the following would be the most appropriate next step in the workup? A. Test the husband with the same CF mutation panel. B. State in the report that the wife is not a carrier. C. Recommend prenatal CF diagnostic testing to the couple. D. Recommend CF testing to the wife’s parents and/or other family members. E. The posttest risk is significantly decreased. There is no need for follow-up.

Answer 37

C. Recommend prenatal CF diagnostic testing to the couple. In this case, the wife may be a carrier, but the definitive conclusion cannot be made until the wife’s parents are tested. Since the wife was pregnant, the first priority is to evaluate the risk of CF for the fetus. Since the husband was a carrier, the fetus would have a significant risk for CF.

Question 38

The chromosome results were normal. The CF 23-mutation panel test showed that the fetus was homozygous for the p.F508del. Which one of the following would be the most appropriate next step in the workup? A. Test the wife and the husband with the same CF mutation panel. B. State that the fetus will be a CF patient with homozygous F508del. C. Sequence the CFTR gene reflex to del/dup with the amniotic fluid sample. D. Sequence the CFTR gene reflex to del/dup with the wife and husband’s peripheral-blood samples. E. Sequence the CFTR gene reflex to del/dup after birth.

Answer 38

C. Sequence the CFTR gene reflex to del/dup with the amniotic fluid sample. Noncystic fibrosis (CF)–causing variants at codons 506, 507, and 508 can cause a false positive result when certain test methods are employed. If the individual is a carrier for I507del, or F508del, and also has the I506V, I507V, or F508C variant on the other chromosome, this situation may lead to a false positive test for homozygosity for the I507del or F508del mutation. The I506V and I507V mutations do not produce a phenotype, while F508C has been associated with congenital bilateral absence of the vas deferens (CBAVD). A male who carries F508del or I507del paired with F508C should be counseled regarding the association of this genotype with male infertility Meng, Haiying. Self-assessment Questions for Clinical Molecular Genetics (p. 249). Academic Press. Kindle Edition.

Question 39

AA 2 wk old with elevated IRT and sweat chloride of 45 mmol/L. Sanger sequencing for cystic fibrosis (CF) found that Johnny was heterozygous for p.F508del and 5T in the CFTR gene. Which one of the following symptoms would Johnny be at risk for? A. Heart failure B. Infertility C. Obesity D. Sudden death E. All of the above F. None of the above

Answer 39

B. Infertility F508del/5T and F508del/R117H are the two most common kinds of compound heterozygote in men with Congenital Bilateral Absence of vas deferens (CBAVD).

Question 40

A panel test for the 23 mutations showed that the fetus was homozygous for the F508del. Which one of the following tests should NOT be included in the reflex test?A. IVS8(T)n B. I506V C. I507V D. F508C

Answer 40

A. IVS8(T)n Noncystic fibrosis (CF)–causing variants at codons 506, 507, and 508 can cause a false positive result when certain test methods are employed. IVS8(T)n, also called 5T/7T/9T,

Question 41

2 wk old AA boy with meconium ileus. Neither of the parents has a family history of cystic fibrosis (CF). What would be the most appropriate test to rule out CF? A. Sequence the CFTR gene reflex to del/dup to Johnny B. Sweat chloride test C. The 23-mutation panel recommended by ACMG D. The 60-mutation panel in the CFTR gene E. The 139-mutation panel in the CFTR gene

Answer 41

B. Sweat chloride test Meconium ileus occurs at birth in 15%–20% of newborns with CF. The first-line diagnosis assay for CF is the sweat chloride test. iontophoresis is used to, whereby one electrode is placed onto the applied medication and an electric current is passed to a separate electrodeAcademic Press. In contrast, people with CF have less thiocyanate and hypothiocyanite in their saliva and mucus.

Question 42

2 wk old AA boy with meconium ileus. A sweat chloride test was positive. Cystic fibrosis (CF) molecular testing found that Johnny was homozygous for one mutation in the CFTR gene. The physician offered ivacaftor for the targeted therapy. Which one of the following mutations would Johnny most likely have? A. F508del B. G542X C. G551D D. 621+1G>T E. W1282X F. N1303K

Answer 42

C. G551D Ivacaftor is Food and Drug Administration (FDA)–approved for patients with G551D mutation, which accounts for 4%–5% of cases of CF.

Question 43

2 wk old AA boy with meconium ileus. A sweat chloride test was borderline (59 mmol/L). Sanger sequencing of the CFTR gene for cystic fibrosis (CF) detected that he had three changes, p.F508del, p.R117H, and 5T. Which one of the following would be the most appropriate next step in the workup? A. Classify the patient as a CF carrier. B. Diagnose the patient as having CBAVD. C. Diagnose the patient as having CF. D. Perform a parental targeted molecular test. E. None of the above.

Answer 43

D. Perform a parental targeted molecular test. The 5T variant paired (in trans) with a CF mutation has been found in men with CBAVD. And R117H mutation can also cause classical CF when in cis with 5T

Question 44

Which one of the following assays should NOT be offered to a couple during pregnancy as a routine cystic fibrosis (CF) carrier screening? A. Sanger sequencing B. The 23-mutation panel C. The 60-mutation panel D. The 139-mutation panel E. None of the above

Answer 44

A. Sanger sequencing Only when CBAVD with negative carrier screening

Question 45

(IRT)/IRT test was positive. The follow-up sweat test in the care center was 45 mmol/L. The DNA test revealed that the infant has G551D, R117H, and 5T variants. The parental targeted molecular genetic test revealed that the R117H and 5T variants in the infant is in cis. Which one of the following would be the most appropriate interpretation? A. The patient does not have CF, so there is no need for follow-up. B. The patient has CF, and treatment should be started right away. C. The patient may have congenital absence of the vas deferens. D. The patient is a CF carrier, and he may develop mild symptoms. E. None of the above.

Answer 45

B. The patient has CF, and treatment should be started right away.

Question 46

2 day old boy with sibling. The DNA test revealed that the infant has F508del and G551D variants. The physician started the treatment immediately. Which would be the most appropriate next step in the workup for the family? A. Recommending targeted molecular genetic testing to the parents B. Recommending targeted molecular genetic testing for the siblings C. Recommending sweat sodium chloride testing to the parents D. Recommending sweat sodium chloride testing for the siblings E. None of the above

Answer 46

D. Recommending sweat sodium chloride testing for the siblings

Question 47

A molecular genetic laboratory receives about 60 samples per week for the cystic fibrosis (CF) carrier test. Which one of the following would be the most common clinical indication for the CF carrier test in this laboratory? A. Prenatal diagnosis B. Postnatal diagnosis C. Diagnostic confirmation after newborn screening D. Family-based testing after proband identification E. Reducing the risk of affected newborns in at-risk populations F. None of the above

Answer 47

E. Reducing the risk of affected newborns in at-risk population (i.e. carrier testing)

Question 48

AJ prenatal testing. Wife has affected brother and unaffected siblings.The husband is a carrier of p.F508del in CFTR found by population-based screening. What is the risk that the couple’s firstborn child will have CF? A. 1/4 B. 1/6 C. 1/16 D. 1/964 E. 1/1928 F. Not clear G. None of the above

Answer 48

B. 1/6 Wife is a carrier 2/3 Husband is a carrier AR risk is 1/4 (2/3)*(1)*(1/4) = 2/12

Question 49

AJ prenatal testing. Wife has affected brother and unaffected siblings. The husband is a carrier of p.F508del in CFTR found by population-based screening. Which test will be the most appropriate for this family as the next step in the workup? A. The ACMG 23-mutation panel with the peripheral-blood sample from the wife B. The ACMG 23-mutation panel with the chorionic villus sampling (CVS) C. The ACMG 23-mutation panel with the amniocentesis sample D. Sanger sequencing analysis of the chorionic villus sampling (CVS) E. Sanger sequencing analysis of the amniocentesis sample F. None of the above

Answer 49

D. Sanger sequencing analysis of the chorionic villus sampling (CVS) The fetus has 2/3×1×1/4=1/6 chance of having CF, since the wife has a 2/3 of chance of being a carrier. With such a high risk, it is it is better to test the fetus to establish a diagnosis. The residual risk of the fetus having CF is still about 1/100 if the result is negative with the 23-mutation panel recommended by the ACMG.

Question 50

AJ preconception testing. Wife has affected brother and unaffected siblings. The husband is a carrier of p.F508del in CFTR found by population-based screening. Which test will be the most appropriate for this family as the next step in the workup? A. The ACMG 23-mutation panel with the peripheral-blood sample from the wife B. The ACMG 23-mutation panel with the chorionic villus sampling (CVS) C. The ACMG 23-mutation panel with the amniocentesis sample D. Sanger sequencing analysis of the chorionic villus sampling (CVS) E. Sanger sequencing analysis of the amniocentesis sample F. None of the above

Answer 50

A. The ACMG 23-mutation panel with the peripheral-blood sample from the wife

Question 51

AJ preconception testing. Wife has affected brother and unaffected siblings. The husband is a carrier of p.F508del in CFTR found by population-based screening. The ACMG 23-mutation panel was offered to the wife, and the result was negative. What is the residual risk that the couple’s firstborn child will have CF? A. 1/4 B. 1/6 C. 1/44 D. 1/385 E. 1/1540 F. Not clear G. None of the above

Answer 51

C. 1/44 Wife is a carrier Prior 2/3 Conditional (1-94%) = 1/20 Joint probability (2/3)*((1/20) = 1/30 Wife is not a carrier Prior 1/3 Conditional 1 Joint = 1/3x 1 = 10/30 Posterior probability 1/30/(1/30+10/30) 1/11 (1/11) x1 x1/4 = 1/44

Question 52

Italian preconception counseling. Wife tested positive for F508del but husband was negative. The follow-up sequencing of the amniotic fluid sample predicted that the fetus would have CF with a compound heterozygous mutations of F508del and c.91C>T(p.R31C). Which one of the following may explain the results? A. It was a laboratory error. The tube was mislabeled. B. The c.91C>T(p.R31C) mutation may be not included in the initial carrier screening mutation panel. C. The c.91C>T(p.R31C) mutation may be a false negative results in the husband because of a genetic variant under the primer and/or probe. D. Based on the mutations identified in the fetus, it was not possible to determine which parent carried the c.91C>T(p.R31C) mutation. E. All of the above. F. None of the above.

Answer 52

E. All of the above.