Other Common Genetic Syndromes Flashcards
What would most likely be the recurrent risk for this family with an affected infant if the patient had a hereditary form of polycystic kidney disease?
A.1/2
B.2/3
C.1/4
D.<1%
E.None of the above
C.1/4
PKD1: (polycystic kidney disease 1) on chromosome 16 80%
PKD2: (polycystic kidney disease 2) on chromosome 4 15%
Adult PCKD with renal, pancreatic and hepatic cysts. Berryaneurysm. What would most likely be the recurrent risk of this disorder in the family?
A.<1%
B.5%–10%
C.25%
D.50%
E.100%
F.None of the above
D.50%
Which one of the following molecular genetics studies would most likely be used as a first-tier test to confirm/rule out genetic etiologies in this adult polycystic kidney disease patient?
A.Chromosomal microarray
B.Multiplex ligation-dependent probe amplification (MLPA)
C.Sequencing the PDK1 and PKD2 genes
D.Sequencing the PKHD1 gene
E.Target variant analysis of the founder pathogenic variants in the PDK1 and PKD2 genes
F.Target variant analysis of the founder pathogenic variants in the PKHD1 gene
G.None of the above
C.Sequencing the PDK1 and PKD2 genes
autosomal dominant chromosomes 16 and 4
PKHD1 autosomal recessive on chromosome 6
Which one of the following polycystic kidney disease does the adult patient most likely have if she has a genetic form of the disorder?
A.De novo autosomal dominant polycystic kidney disease
B.Inherited autosomal dominant polycystic kidney disease
C.De novo autosomal recessive polycystic kidney disease
D.Inherited autosomal recessive polycystic kidney disease
E.None of the above
B.Inherited autosomal dominant polycystic kidney disease
Pt with adult PCKD. Of the family members who are potential kidney donors, only her youngest sister, age 25 years, is a good tissue match. This sister is evaluated by ultrasound, CT, and MRI as parts of comprehensive renal image analysis, and the results are negative. Which one of the following is the most appropriate next step in the workup?
A.Considering transplantation with a kidney from an unrelated donor
donor
B.Considering transplantation with a kidney from the brother
C.Considering transplantation with a kidney from the youngest sister
D.Considering transplantation with a kidney from a relative without pathogenic variant
E.Considering transplantation with a kidney from the youngest if she does not have a pathogenic variant
F.None of the above
E.Considering transplantation with a kidney from the youngest if she does not have a pathogenic variant
Pt with adult PCKD with no identified mutation. Of the family members who are potential kidney donors, only her youngest sister, age 25 years, is a good tissue match. This sister is evaluated by ultrasound, CT, and MRI as parts of comprehensive renal image analysis, and the results are negative. Which one of the following is the most appropriate next step in the workup?
A.Considering transplantation with a kidney from an unrelated donor
donor
B.Considering transplantation with a kidney from the brother
C.Considering transplantation with a kidney from the youngest sister
D.Considering transplantation with a kidney from a relative without pathogenic variant
E.Considering transplantation with a kidney from the youngest if she does not have a pathogenic variant
F.None of the above
A.Considering transplantation with a kidney from an unrelated donor
donor
-linkage analysis not viable since only affected family member
- sibling should be considered at risk
Which one of the following genes would most likely harbor a pathogenic variant if the patient had autosomal dominant polycystic kidney disease (ADPKD)?
A.PKD1
B.PKD2
C.PKHD1
D.None of the above
A.PKD1
Because of a paternal history of bilateral renal cysts, genetic testing of PKD1 and PKD2 was ordered, and a 3-bp deletion, c.1602_1604TGT, was detected in the PKD2 coding region. Targeted molecular analysis of the father detected the same deletion. Which one of the following mechanisms would most likely contribute to the pathogenesis of the ADPKD in this patient?
A.Dominant negative
B.Gain of function
C.Loss of function
D.None of the above
C.Loss of function
Communication with the laboratory that sent the sample confirmed the presence of the c.3817C>T, but not the 15-bp deletion in exon 3. Dr. Z sent this sample to a third clinical laboratory for Sanger sequencing, and the result confirmed the presence of the c.3817C>T, but not the 15-bp deletion in exon 3. Which one of the following mechanisms would most likely contribute to the discrepancy of the testing results with the same specimen in this case?
A.Interference of pseudogenes
B.Primers in polymorphic regions
C.Sample mess-up
D.Variation of enrichment methods
E.None of the above
A.Interference of pseudogenes
Which one of the following genes would most likely harbor a pathogenic variant in a neonate (without FHx for 3 generations) if the patient had a hereditary form of polycystic kidney diseases?
A.PKD1
B.PKD2
C.PKHD1
D.None of the above
C.PKHD1
Compound heterozygous pathogenic variants, c.10444C>T and c.5909–2delA, were detected in the PKHD1 gene in a neonate. Which one of the following would be the most appropriate next step in the workup for this family?
A.Counseling the family about the 25% recurrent risk
B.Recommending prenatal testing for future pregnancies
C.Testing the couple for the pathogenic variants
D.Testing the husband for the pathogenic variants
E.Testing the wife for the pathogenic variants
F.All of the above
G.None of the above
v
The physician suspected that the patient had tuberous sclerosis and autosomal dominant polycystic kidney disease (ADPKD). Which one of the following molecular genetics assays would be most appropriate for this patient to confirm the diagnosis?
A.Multiplex ligation-dependent probe amplification (MLPA)
B.Next-generation sequence (NGS)
C.Quantitative PCR
D.Restriction-fragment–length polymorphism
E.Sanger sequencing
F.None of the above
A.Multiplex ligation-dependent probe amplification (MLPA)
MLPA is an appropriate technique to detect deletions/duplications for TSC2/PKD1 contiguous gene deletion syndrome
A molecular genetics study was ordered to confirm/rule out genetic etiology, and pathogenic variant(s) were identified. Which one of the following genes would most likely harbor the pathogenic variant(s) in this patient?
A.PKD1
B.PKD2
C.PKD3
D.PKHD1
E.PKHD1L1
A.PKD1
26 yo with clinical symptoms presents for sequencing based on FHx. The results showed a homozygous pathogenic variant, c.3817C>T(p.Gln1273Ter), in PKD1. Which one of the following would be the most appropriate interpretation of the result?
A.The c.3817C>T(p.Gln1273Ter) variant is pathogenic. The patient had polycystic kidney disease.
B.The parents of the proband may be related. The patient needs to be monitored closely for early-onset disease.
C.The result is questionable. The variant needs to be reanalyzed with another pair of primers.
D.The result is questionable. The lab should ask for a redraw of a peripheral-blood sample from the patient.
E.None of the above.
D.The result is questionable. The lab should ask for a redraw of a peripheral-blood sample from the patient.
In adult dominant autosomal dominant PCKD – two homozygous mutations is questionable
Infant with affected sister has pathogenic variant(s) for ADPKCD were identified. Which one of the following genes would most likely harbor the pathogenic variant(s) in this family?
A.PKD1
B.PKD2
C.PKD3
D.PKHD1
E.PKHD1L1
D.PKHD1
Which one of the following statements regarding polycystic kidney diseases is correct?
A.Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are caused by same genes. B.ADPKD usually causes more significant renal- and liver-related morbidity and mortality than ARPKD.
C.The onset of ADPKD is usually earlier than that of ARPKD.
D.The severity of ADPKD disease is attributed primarily to locus heterogeneity.
E.The contiguous gene deletion syndrome including symptoms for both ADPKD and tuberous sclerosis typically results from a deletion involving both PKD2 and TSC1.
D.The severity of ADPKD disease is attributed primarily to locus heterogeneity.
PKD1 and TSC2 (tuberin) on Chr 16
PKD2 on Chr 4 and TSC1 on chromosome 9
Which one of the following statements regarding polycystic kidney diseases is correct?
A.The contiguous gene deletion syndrome including symptoms for both ADPKD and tuberous sclerosis typically results from a deletion involving both PKD1 and TSC1.
B.The contiguous gene deletion syndrome including symptoms for both ADPKD and tuberous sclerosis typically results from a deletion involving both PKD1 and TSC2.
C.The contiguous gene deletion syndrome including symptoms for both in ADPKD and tuberous sclerosis typically results from a deletion involving both PKD2 and TSC1.
D.The contiguous gene deletion syndrome including symptoms for both ADPKD and tuberous sclerosis typically results from a deletion involving both PKD2 and TSC2.
E.None of the above.
B.The contiguous gene deletion syndrome including symptoms for both ADPKD and tuberous sclerosis typically results from a deletion involving both PKD1 and TSC2.
16p13.3,
A 28-year-old Caucasian man has been evaluated as a potential living-relative kidney donor for his mother (see the figure below for the pedigree). He is apparently healthy. Renal ultrasonography results were negative. The PKD1 and PKD2 studies for autosomal dominant polycystic kidney disease (ADPKD) did not identify pathogenic variants in the mother. Which one of the following is the most appropriate next step in the workup for this family?
A.Excluding the patient as a renal donor for his mother
B.Performing linkage analysis in the family
C.Sequencing the patient for an ADPKD pathogenic variant
D.Testing PKHD1 for autosomal recessive polycystic kidney disease (ARPKD)
E.Using a more sensitive renal imaging method, such as MRI or CT F.None of the above
B.Performing linkage analysis in the family
MPLA -
A 4-year-old Caucasian boy was admitted to a local hospital for “febrile seizures.” An initial evaluation revealed nystagmus and pigmentary retinopathy, mild central obesity, hypogonadism, mental retardation, behavioral abnormalities, hypothyroidism, hypertension, and severe anemia. He had postaxial polydactyly. Ultrasonography revealed bilateral multiple renal cysts. He was the second offspring of consanguineous parents. His family history was notable for obesity, learning difficulties, six digits on both hands, and visual impairment in his 14-year-old sister; the etiology was unknown. Which one of the following pathogenic variants would this patient most likely have?
A.c.107C>T(p.T36M) in PKHD1
B.c.12258T>A(p.C4086X) in PKD1
C.c. 547A>G(p.G72S) in BBS5
D.46,XX,der(16)t(X;16)(q28;p13.2)
E.None of the above
C.c. 547A>G(p.G72S) in BBS5
Bardet–Biedl syndrome (BBS). cilia complex - 19 genes
The medical geneticist suspected that the patient had Bardet–Biedl syndrome and ordered a molecular genetics study to confirm the diagnosis. Which one of the following molecular technologies would provide the most cost-effective testing strategy for this patient?
A.Next-generation sequencing (NGS)
B.Quantitative real-time PCR
C.Restriction-fragment–length polymorphism (RFLP)
D.Sanger sequencing
E.None of the above
A.Next-generation sequencing (NGS)
The medical geneticist suspected that the patient had Bardet–Biedl syndrome and ordered a next-generation sequencing (NGS) panel to confirm the diagnosis, which includes 19 genes. Which of the following is this an example of?
A.Allelic heterogeneity
B.Cellular heterogeneity
C.Incomplete penetrance
D.Locus heterogeneity
E.Variable expression
F.None of the above
D.Locus heterogeneity
AR Bardet–Biedl syndrome (BBS): BBS1, BBS2, ARL6 (BBS3), BBS4, BBS5, MKKS (BBS6), BBS7, TTC8 (BBS8), BBS9, BBS10, TRIM32 (BBS11), BBS12, MKS1 (BBS13), CEP290 (BBS14), WDPCP (BBS15), SDCCAG8 (BBS16), LZTFL1 (BBS17), BBIP1 (BBS18), and IFT27 (BBS19). Approximately 20% of persons with BBS do not have identifiable pathogenic variants in any of the 19 known BBS-related genes;
cilia complex
Which one of the following would most likely be the recurrent risk of the same condition in the family if Jerry (microscopic hematuria and and his cousin had a hereditary form of renal diseases?
A.10%
B.25%
C.50%
D.75%
E.99%
F.Unpredictable
B.25%
X-linked Alport syndrome
recurrent risk 1/2×1/2=1/4 COL4A5
Dr. Z. suspects that Mrs. J. has early-onset Alzheimer disease. Which one of the following genes is NOT associated with autosomal dominant early-onset Alzheimer disease?
A.APOE
B.APP
C.PSEN1
D.PSEN2
E.All of the above
F.None of the above
A.APOE
LOAD
The APOE ε4 allele is the most significant risk factor, while the APOE ε2 allele is protective.
The physician diagnosed the Finnish patient clinically with Alzheimer disease and ordered a molecular genetics study for it. Which one of the following molecular technologies would provide the cost-effective testing strategy for this patient?
A.Multiplex ligation-dependent probe amplification (MLPA)
B.Next-generation sequencing (NGS)
C.Quantitative real-time PCR D.Restriction-fragment–length polymorphism (RFLP)
E.Sanger sequencing
F.None of the above
A.Multiplex ligation-dependent probe amplification (MLPA)
A 4555-bp deletion spanning exon 9 of PSEN1 has been found in the Finnish population with founder effect; this mutation is rarely observed in other populations