Clinical genetics

Question 1

Among the following monogenic diseases predisposing for tumorigenesis which one is not autosomal dominantly inherited?
A) multiple endocrine neioplasia type 1
B) von Hippel–Lindau disease
C) ataxia teleangiectasia
D) multiple endocrine neioplasia type 2
E) neurofibromatosis type 1

Answer 1

C) ataxia teleangiectasia

Question 2

At which pregnancy age is amniocentesis recommended?
A) 4–6 weeks
B) 10–12 weeks
C) 15–17 weeks
D) 20–22 weeks
E) 24–26 weeks

Answer 2

C) 15–17 weeks

Question 3

Among the following chromosome abnormalities which one is the most frequent?
A) Turner-syndrome
B) Edwards-syndrome
C) Down-syndrome
D) Patau-syndrome
E) Williams-syndrome

Answer 3

C) Down-syndrome

Question 4

What does the term penetrance mean?
A) the frequency of a genetic alteration
B) the frequency of a certain phenotype int he case of a certain genotype
C) a form of genetic regulation
D) the expression of small molecular weight RNAs
E) region of chromosomal regulation

Answer 4

B) the frequency of a certain phenotype int he case of a certain genotype

Question 5

What proportion of the human genome is protein-coding?
A) 3%
B) 10%
C) 25%
D) 40%
E) 60%

Answer 5

A) 3%

Question 6

Which one of the following diseases has the lowest penetrance?
A) multiple endocrine neoplasia type 1
B) multiple endocrine neoplasia type 2
C) neurofibromatosis type 1
D) cystic fibrosis
E) haemochromatosis

Answer 6

E) haemochromatosis

Question 7

Which one of the following diseases does not predispose to pheochromocytoma?
A) von Hippel–Lindau disease
B) Gardner syndrome
C) multiple endocrine neoplasia type 2
D) neurofibromatosis type 1
E) inherited paraganglioma syndromes

Answer 7

B) Gardner syndrome

Question 8

By definition, what is the frequeny of a mutation?
A) < 1%
B) < 5 %
C) < 10%
D) < 20%
E) < 30%

Answer 8

A) < 1%

Question 9

What does the term compound heterozygosity mean?
A) More mutations are responsible for a certain disease in autosomal dominantly inherited syndrome.
B) The importance of Y chromosome alterations in sex-linked inheritance.
C) In the case of autosomal recessively inherited disease, different mutations on different allelles of the same gene are jointly responsible for the develeopment of the disease.
D) A rare regulatory mechanism in the case of X-linked dominant inheritance
E) The emergence of different pheotypes due to different mutations int he case of autosomal recessively inherited diseases.

Answer 9

C) In the case of autosomal recessively inherited disease, different mutations on different allelles of the same gene are jointly responsible for the develeopment of the disease.

Question 10

Which pattern of inheritance is characteristic to blood relation between parents?
A) autosomal dominant
B) autosomal recessive
C) X-linked dominant
D) X-linked recessive
E) polygenic

Answer 10

B) autosomal recessive

Question 11

What is the chance of the emergence of an autosomal recessively inherited disease in the offspring of two heterozygote carriers?
A) 10%
B) 25%
C) 40%
D) 50%
E) 60%

Answer 11

B) 25%

Question 12

What is the chance of emergence of an autosomal dominantly inherited disease in one child of an affected heterozygote individual?
A) 10%
B) 25%
C) 40%
D) 50%
E) 60%

Answer 12

D) 50%

Question 13

For which mode of inheritance is the following statement true: of the offspring of an affected male and a healthy female, all sons are healthy and all daughters are affected?
A) X-linked recessive
B) X-linked dominant
C) autosomal recessive
D) autosomal dominant
E) polygenic

Answer 13

B) X-linked dominant

Question 14

Among the following diseases, in which case does genomic imprinting not constitute to the pathogenesis?
A) Prader–Willi syndrome
B) Angelman syndrome
C) Beckwith–Wiedemann syndrome
D) cystic fibrosis

Answer 14

D) cystic fibrosis

Question 15

Over what frequency of occurrence in the general population is a genetic variant considered a polymorphism?
A) 1%
B) 7%
C) 10%
D) 15%
E) 20%

Answer 15

A) 1%

Question 16

The trisomy of which chromosome is the most frequent in live-born new-borns?
A) 13
B) 17
C) 19
D) 21
E) 22

Answer 16

D) 21

Question 17

Which chromosomal abnormality affecting the sex chromosomes has the highest incidence?
A) Turner syndrome
B) Klinefelter syndrome
C) Triple X sydrome (superfemale)
D) 46XX male
E) 46XY female

Answer 17

B) Klinefelter syndrome

Question 18

For which listed chromosome abnormality are the following symptoms characteristic: immunodeficiency, hypoparathyroidism, congenital heart defect?
A) Cri du chat syndrome
B) DiGeorge syndrome
C) Down syndrome
D) Turner syndrome
E) Prader–Willi syndrome

Answer 18

B) DiGeorge syndrome

Question 19

Which one of the following symptoms is not characteristic to Turner syndrome?
A) short stature
B) streak gonad
C) primary amenorrhea
D) asthma bronchiale
E) coarctation of the aorta

Answer 19

D) asthma bronchiale

Question 20

Amog the following diseases which one is not autosomal dominantly inherited?
A) Marfan syndrome
B) cystic fibrosis
C) Huntington’s disease
D) familial adenomatosus polyposis
E) hereditary retinoblastoma

Answer 20

B) cystic fibrosis

Question 21

Which statement is false for phenylketonuria?
A) autosomal recessively inherited
B) it is the consequence of mutations of the gene encoding phenylalanine hydroxylase
C) the main symptoms are diarrhea and secondary malabsorption
D) elevated phenylalanine levels cause severe neurological symptoms
E) it is screened routinely in new-borns

Answer 21

C) the main symptoms are diarrhea and secondary malabsorption

Question 22

Which one of the following hereditary metabolic diseases affect purine metabolism?
A) Tay–Sachs disease
B) Niemann–Pick disease
C) Hurler syndrome
D) Rett syndrome
E) Lesch–Nyhan syndrome

Answer 22

E) Lesch–Nyhan syndrome

Question 23

Which one of the following statements is false for cystic fibrosis?
A) the most common fatal autosomal recessive disorder among Caucasian race
B) the frequency of carriers is 1/25
C) the frequency of carriers is 1/500
D) it is the consequence of mutations of a protein involved in the transport of chloride ions.
E) ΔF508 is the most common mutation.

Answer 23

C) the frequency of carriers is 1/500

Question 24

Which one of the following symptoms is not characteristic of cystic fibrosis?
A) chronic obstructive pulmonary disease
B) deficiency of the exocrine pancreas
C) diabetes mellitus
D) meconium ileus in new-borns.
E) male infertility due to absence of vas deferens

Answer 24

C) diabetes mellitus

Question 25

Which one of the following is false regarding Duchenne muscular distrophy?
A) X-linked recessive inheritance
B) it is the consequence of mutations of the largest human protein, dystrophin
C) one manifestation is the pseudohypertrophy of the calves
D) weakness of the muscles begins in adulthood
E) elevated serum levels of creatine kinase

Answer 25

D) weakness of the muscles begins in adulthood

Question 26

Which of the following statements is false for Huntington’s disease?
A) it belongs to trinucleotide repeat disorders
B) it follows autosomal dominant inheritance
C) the disease manifestates in adulthood, usually after 40 years of age
D) one manifestation is severe hypertension
E) during familial inheritance, the first symptoms presents at earlier age in the offspring of the affected father (anticipation)

Answer 26

D) one manifestation is severe hypertension

Question 27

Which of the following disorder is not a trinucleotide repeat disorder?
A) fragile X syndrome
B) myotonic dystrophy
C) Huntington’s disease
D) Friedreich’s ataxia
E) Rett syndrome

Answer 27

E) Rett syndrome

Question 28

Which one of the following is not characteristic to diseases of the mitochondrial DNA?
A) they can be inherited from the mother and from the father
B) by a main rule, they can be inherited only from the mother
C) main characteristics include the disorders of the nervous system (including the sensory nervous system) and the muscle system
D) there may be wide phenotype variability
E) heteroplasmy is one of the main reasons of phenotype variability

Answer 28

A) they can be inherited from the mother and from the father

Question 29

Which following characteristic is false for acute intermittent porphyria?
A) autosomal dominant inheritance
B) high penetrance
C) mutations of porphobilinogen deaminase are responsible for the disease
D) severe abdominal pain which cannot be explained by organic reasons
E) vegetative nervous system is often affected

Answer 29

B) high penetrance

Question 30

Which apolipoprotein E allele is linked to Alzheimer’s disease?
A) APOA
B) APOC
C) APOE1
D) APOE2
E) APOE4

Answer 30

E) APOE4

Question 31

Which of the following vitamin’s deficiency has been mostly associated with the development of neural tube defects?
A) vitamin B1
B) vitamin B2
C) folic acid
D) vitamin C
E) vitamin A

Answer 31

C) folic acid

Question 32

Which hereditary tumor syndrome does not predispose to breast cancer?
A) Li-Fraumeni syndrome
B) mutations of BRCA1 gene
C) mutations of BRCA2 gene
D) von Hippel–Lindau disease
E) Cowden syndrome

Answer 32

D) von Hippel–Lindau disease

Question 33

Which of the following syndromes is not associated with chromosomal instability arising from deficient DNA repair?
A) neurofibromatosis type 1
B) ataxia teleangiectasia
C) Bloom syndrome
D) xeroderma pigmentosum
E) Fanconi anemia

Answer 33

A) neurofibromatosis type 1

Question 34

At which pregnancy age is chorionic villus sampling recommended to be performed?
A) 4–6 weeks
B) 10–12 weeks
C) 14–16 weeks
D) 18–20 weeks
E) 24–26 weeks

Answer 34

B) 10–12 weeks

Question 35

When is prenatal diagnostical procedures recommended?
A) advanced maternal age
B) de novo chromosome abnormality in the previous child
C) one parent carries structural chromosomal alteration
D) in all three of the previous cases
E) none of the previous cases

Answer 35

D) in all three of the previous cases

Question 36

Which of the following disorders cannot be detected by fetal utrasound imaging?
A) holoprosencephaly
B) neural tube defects
C) omphalocele
D) Huntington’s disease
E) cystic hygroma

Answer 36

D) Huntington’s disease

Question 37

Which two chromosomes are affected by translocation in the case of Philadelphia chromosome?
A) 9 and 22
B) 8 and 14
C) 9 and 14
D) 8 and 22
E) 10 and 14

Answer 37

A) 9 and 22

Question 38

Which one of the following is not a characteristic of the fragile X syndrome?
A) it causes moderate mental retardation in affected boys and mild mental retardation in affected girls
B) it belongs to trinucleotide repeat disorders
C) enlarged testicles is a characteristic of the disease in affected boys
D) congenital heart defects are fequently observed
E) the disease is the consequence of FMR1 gene mutations

Answer 38

D) congenital heart defects are fequently observed

Question 39

Which one of the following is not a characteristic of glucose-6-phosphate dehydrogenase deficiency?
A) X-linked recessive inheritance
B) frequently observed in Mediterranean countries
C) predisposes to hemolytic anemia in homozygotes
D) mental retardation is frequent
E) heteroygosity may have a protective effect against malaria

Answer 39

D) mental retardation is frequent

Question 40

Which of the following diseases is inherited in autosomal dominant manner?
A) multiple andocrine neoplasia type 1
B) neurofibromatosis type 1
C) von Hippel–Lindau disease
D) all three of them
E) neither of them

Answer 40

D) all three of them

Question 41

Which chromosome is affected in Prader-Willi syndrome?
A) 3
B) 12
C) 15
D) 17
E) 19

Answer 41

C) 15

Question 42

Which of the following is false for Tay-Sachs disease?
A) lysosomal storage disease
B) Lisch nodules of the iris is a characteristic
C) cherry-red spot on the retina is a characteristic
D) neurodegenerative disease
E) hexosaminidase A deficiency plays a role int he pathogenesis

Answer 42

B) Lisch nodules of the iris is a characteristic

Question 43

Which of the following is the most severe manifestation of thalassaemia?
A) HbH disease
B) hydrops fetalis
C) hemolytic anemia
D) cerebral infarction
E) extramedullary hematopoiesis

Answer 43

B) hydrops fetalis

Question 44

Associate the following symptoms with the appropriate monogenic disease!
A) Marfan syndrome
B) cystic fibrosis
C) haemophilia (A and B)
D) Duchenne muscular dystrophy
E) Huntington’s disease

INT - 16.46 - hemorrhagic diatheses, hemarthrosis, decisively boys are affected
INT - 16.47 - manifestates in adulthood, severe neurodegenerative disease, autosomal dominantly inherited
INT - 16.48 - Severe muscle weakness, pseudohypertrophy of the calves, mild mental retardation, X-linked inheritance
INT - 16.49 - Chronic obstructive pulmonary disease, pancreatic deficiency, meconium ileus in new-borns, infertility secondary to the atresia of the vas deferens
INT - 16.50 - tall, dysmorphic stature, alterations of the skeletal structure, ectopic eyepiece, mitral valve prolapse, dilation and rupture of the aorta

Answer 44

46- C
47- E
48- D
49- B
50- A

Question 45

Associate the following symptoms with the appropriate monogenic tumor syndrome!
A) multiple endocrine neoplasia 2A
B) neurofibromatosis type 1
C) von Hippel–Lindau disease
D) Li–Fraumeni syndrome
E) multiple endocrine neoplasia type 1

INT - 16.51 - clear cell renal cell carcinoma, pheochromocytoma, retinal and cerebellar hemangioblastoma, pancreatic cysts and neuroendocrine tumor
INT - 16.52 - parathyroid hyperplasia, endocrine pancreatic tumors, pituitary adenoma
INT - 16.53 - medullary thyroid cancer, pheochromocytoma, hyperparathyroidism
INT - 16.54 - neurofibroma, neurofibrosarcoma, brain tumor, pheochromocytoma
INT - 16.55 - breast cancer, brain tumor, adrenocortical cancer, sarcomas, leukemia

Answer 45

51- C
52- E
53- A
54- B
55- D

Question 46

Associate the following symptoms with the appropriate chromosomal diseases!
A) Prader–Willi syndrome
B) Turner syndrome
C) Down syndrome
D) Klinefelter syndrome
E) Edwards syndrome

INT - 16.56 - Mental retardation, severe developmental disorder, congenital heart defects, prominent occiput, abnormally small jaw, low-set, malformed ears, affected individuals rarely survive beyond childhood
INT - 16.57 - mental retardation, short stature, brachycephaly, flat nape, epicanthic fold, congenital heart defects
INT - 16.58 - Primary hypogonadism, infertility, tall stature, gynecomastia
INT - 16.59 - hypotonia and poor feeding during infancy, which turns to hyperphagia and extreme obisity during childhood, disproportionally smaller hands and toes, cognitive disturbancies, reproductive sterility
INT - 16.60 - Short stature, shield chest, webbed neck, streak gonad, cardiovascular malformations

Answer 46

56- E
57- C
58- D
59- A
60- B

Question 47

Associate the following patterns of inheritance with the characteristics!
A) autosomal recessive
B) autosomal dominant
C) X-linked recessive
D) X-linked dominant
E) polygenic, multifactorial inheritance

INT - 16.61 - From the relationship of affected males and healthy females all daughters are affected, while all sons are healthy. 50% of an affected female’s children may inherit the disease irrespective of the child’s sex.
INT - 16.62 - Familial history of the disease is a characteristic, however the pattern of inheritance does not follow monogenic Medelian inheritance. Emergence of the disease is more common in closer than further relatives of an affected individual.
INT - 16.63 - The disease is much more common in males. All daughters of an affected male will be carrier, while all sons will be healthy. Heterozygote females are usually healthy, however manifestations to some extent may be present.
INT - 16.64 - Typically, affected individuals are present in all generations. Every child of an affected individual has 50% chance to inherit the disease irrespective of sex. These diseases are less likely to alter life expectancy.
INT - 16.65 - These diseases are usually severe. Some generations do not have affected individuals. Blood relations are common in the family history of the affected families. Males and females are affected in the same frequency.

Answer 47

61- D
62- E
63- C
64- B
65- A

Question 48

Associate the following therapeutical approaches to the following genetic diseases!
A) dietary restrictions
B) enzyme replacement therapy
C) hormone replacement therapy
D) inhibitor administration
E) replacement of a specific protein (not enzyme)

INT - 16.66 - congenital hypothyroidism
INT - 16.67 - haemophilia A and B
INT - 16.68 - familial hypercholesterolemia
INT - 16.69 - Gaucher’s disease (glucocerebrosidase deficiency)
INT - 16.70 - α-1 antitrypsin deficiency
INT - 16.71 - phenylketonuria
INT - 16.72 - galactosemia

Answer 48

66- C
67- E
68- D
69- B
70- E
71- A
72- A

Question 49

Associate the following sexual developmental disorders with the characteristics!
A) testicular feminization (Morris syndrome)
B) 21-hidroxylase deficiency (congenital adrenal hyperplasia)
C) Turner syndrome
D) Klinefelter syndrome

INT - 16.73 - Classical forms are associated with 45X0 kariotype.
INT - 16.74 - Disease is due to mutations of the androgen receptor.
INT - 16.75 - Serum levels of 17α-hydroxyprogesterone are elevated.
INT - 16.76 - The most frequent disorder affecting sex chromosomes.

Answer 49

73- C
74- A
75- B
76- D

Question 50

Associate the chance of the birth of affected child with the folowing cases (assume maximal penetrance)!
A) 25%
B) 50%
C) 100%
D) 0%

INT - 16.77 - In the daughters of an affected male and a healthy female in X-linked dominant inheritance
INT - 16.78 - In the relationship of two heterozygote in autosomal recessive inheritance
INT - 16.79 - In the relationship of an affected heterozygote and a healthy individual in autosomal dominant inheritance
INT - 16.80 - In the sons of an affected male and a healthy female in X-linked recessive inheritance.

Answer 50

77- C
78- A
79- B
80- D