Genetics

Question 1

What effect does Down syndrome have on the quadruple test?

Answer 1

Decreased alphafetoprotein
decreased PAPP-A
increased human chorionic gonadotrophin
decreased unconjugated estriol
increased inhibin

raised nuchal translucency is noted

Question 2

What is the earliest appropriate gestational age to perform CVS?

Answer 2

11 weeks

Question 3

A woman has been diagnosed with carrying the BRCA1 gene. What is her lifetime risk of breast cancer?

Answer 3

The answer is 60 - 90%. BRCA2 has a lifetime risk of breast carcinoma of 45 - 80%.

Question 4

A woman has been diagnosed with carrying the BRCA1 gene. What is her lifetime risk of ovarian cancer?

Answer 4

The answer is 40-60 %. BRCA2 has a lifetime risk of ovarian cancer at 10-30%.

Question 5

A teenage boy has increased in height at puberty and is now taller than all the other males in his family, but he is concerned because his testicles seem to be smaller than normal. On examination he also has gynaecomastia .Diagnostic tests reveal that the man has azoospermia, testicular atrophy and gynaecomastia.

Which is the most likely genetic cause? cause?

Answer 5

The presentation is compatible with Klinefelter’s syndrome, which is 47XXY due to nondisjunction during meiosis. It has an incidence of 1 in 650 males.

The karyotype in this case is normally 47 XXY. The other variants that present are XXYY or XXXY.

Question 6

A baby is born with renal abnormalities, omphalocele, holoprosencephaly and polydactyly.

Which genetic syndrome is likely to be diagnosed?

Answer 6

Patau (trisomy 13)

Question 7

If both parents carry the trait for beta thalassaemia, what is the chance of a female baby having beta thalassaemia?

Answer 7

25%

Question 8

A teenage girl presents with primary amenorrhoea and delayed puberty. Further investigations reveal that her karyotype is 45 XO.

Which condition does the teenager have?

Answer 8

Turner syndrome is the most common cause of gonadal dysgenesis. In the most severe form it is associated with the following features: short stature, webbing of the neck, cubitus valgus, widely spaced nipples and cardiac and renal abnormalities. Spontaneous menstruation may occur due to mosaicism, but premature ovarian failure is more common. Low-dose estrogen therapy is beneficial to promote puberty changes. Long-term hormone replacement is essential to prevent osteoporosis.

Congenital adrenal hyperplasia has a normal female karyotype and the aetiology is due to an enzyme deficiency. Down syndrome is associated with trisomy 21.

Androgen insensitivity syndrome has a normal 46XY karyotype and the syndrome is due to failure of development of Wolffian structures as a result of insensitivity to testosterone.

Mayer-Rokitansky-Küster-Hauser syndrome has 46 XX karyotype. There is a developmental defect due to lack of fusion of the müllerian ducts. The patient will have a uterine remnant and a blind vagina.

Question 9

Which chromosomal abnormality has a known association with severely impaired semen quality?

Answer 9

The answer is microdeltions of the Y chromosomes.

Question 10

Which error in meiosis is the most common cause of Down syndrome?

Answer 10

Nondisjunction

In addition to recognisable facial features, mental retardation and short stature, these individuals also exhibit congenital heart defects (atrioventricular septal defect), hearing loss, duodenal obstruction and immune system defects.

Question 11

What cells in the spermatogenesis process can undergo mitotic division?

Answer 11

Spermatogonia/oogonium

Question 12

Male infertility in a patient with cystic fibrosis is likely to be due to which condition?

Answer 12

Congenital absence of vas deferens

Question 13

A woman who is about to have an evacuation of uterus for her third miscarriage asks if the placental tissue can be tested for karyotype.

Which is the most common autosomal trisomy found in early pregnancy loss?

Answer 13

Trisomy 16 is the most common trisomy seen in miscarriage, accounting for at least 15% of first-trimester pregnancy losses.

Question 14

Non-invasive prenatal testing (NIPT) on maternal blood is available to screen for trisomies 13, 18 and 21 as well as other genetic conditions and fetal Rhesus D status.

In which circumstance can the NIPT test results be unreliable?

Answer 14

Maternal obesity

Question 15

What are the most common genotypes of a partial mole?

Answer 15

69XXY/ 69XXX / 69XYY

Question 16

‘Cri du chat’ is a genetic condition where the infant has a weak cat-like cry, microcephaly, severe mental retardation and congenital heart disease.

Which type of genetic alteration is responsible for this condition?

Answer 16

Partial deletion

Question 17

Most abnormalities of chromosome structure are due to breakage followed by reconstitution in an abnormal combination. There are two structural re-arrangements of genetic material which are likely to be transmitted from parent to child.

Which two structural alterations can be transmitted?

Answer 17

Inversion and translocation

Question 18

Some women with Lynch syndrome have a germline mutation which confers an increased risk of early-onset cancer (including colorectal, endometrial, ovarian, gastric, small bowel, hepatobiliary, brain, ureteric and renal pelvic).

Which gene is faulty in Lynch syndrome?

Answer 18

DNA mismatch repair (MMR) gene

Question 19

When they can be visualised, chromosomes can be described in terms of the position of the centromere.

During which part of mitosis does the chromatin condense and become visible at high magnification through a light microscope?

Answer 19

Prophase

Question 20

What is the commonest genotype associated with a complete mole?

Answer 20

46 XX

Question 21

In tuberous sclerosis, tumours grow in the brain and other organs. A third of cases are inherited.

What is the mode of inheritance of tuberous sclerosis?

Answer 21

Autosomal dominant

Question 22

A 12-year-old girl presents at menarche with menorrhagia and testing reveals that she is a haemophilia A carrier.

What is the risk of any future male offspring being affected by the condition?

Answer 22

50%

X-linked recessive inheritance. Haemophilia A involves low Factor VIII levels due to a mutation on the X chromosome.

Question 23

What does aneuploidy mean?

Answer 23

Cell has chromosomes that are not an exact multiple of haploid.

Aneuploidy is an abnormal number of chromosomes in a cell e.g. 47 chromosomes in trisomy 21; 45 chromosomes in Turner syndrome 45XO.

Question 24

A couple attend clinic for investigation following three consecutive first trimester miscarriages.

What parental chromosomal abnormality is associated with recurrent miscarriage?

Answer 24

Robertsonian balanced translocations

Question 25

Which alleles code for Rhesus status?

Answer 25

C, D and E. The 15% of the population who are rhesus negative have the genotype cde.