MCM 2-31 Numerical & Structural Abnormalities

Question 1

XXX female prevalence and cause?

XYY male prevalence and cause?

Klinefelter syndrome prevalance and cause?

Answer 1

1/1000 female live births, maternal meiosis I error

1/1000 male live births, paternal meiosis I error

klinefelter is 47,XXY
1/1000 live male births, tall and thin.
50% caused by meiosis I error in father

Question 2

most common recognized sex chromosome aneuploidy in females?

phenotype?
prevalence?
symptoms?

Answer 2

Turner syndrome: 45,x

highly variable phenotype
1/5000 female births

webbed neck, short, no menses

Question 3

10% of Turner syndrome patients are?

concern?

Answer 3

mosaics or either 45,x/46XX or 45,x/46,xy

individuals who have a partial or complete Y chromosome in one cell live have increased risk for gonadoblastoma

Question 4

chromosomal rearrangement types. Who is at risk for each?

Answer 4

balanced : all material present but rearranged (patient likely OK, offspring at risk)

unblanaced: some material is missing or duplicated (bad for patient)

Question 5

deletion is what? leads to?

Answer 5

loss of a part of chromosome

partial monosomy

Question 6

duplication is what? leads to?

Answer 6

additional copy of a chromosome segment

results in partial trisomy

Question 7

examples of deletion syndroms

Answer 7

williams-beuren syndrome

prader-willi

miller-dieker

Velocardiofacial syndrome

Question 8

robertson translocation

Answer 8

centomere to centrometre translocation involving acrocentric (centromere at tio) chromosomes leading to fusion

if passed on in gametes, problem.

involves chromsomes with centromeres at end, attatch end-to-end. May be perfectly normal and only have 45 chromosomes because 2 are togther. The eggs/sperm may have extra/not engouh or one or antoehr.

Question 9

williams-beuren syndrome

Answer 9

7q11.23.23 genes

suprevalvicular aortic stenosis
thickening of skin
skeletal and joint limitations
renal anomolies
low IQ
excellent music skills, terrible at math
outgoing and friendly

BLUE SCLERA, stellate iris

Question 10

velocardiofacial syndrome (VCFS) cause? Fish signals?

Answer 10

3mb deletion on chr.22
FISH

normal individual has 2 signals per chromosome (22),

VCFS patient will have one chromosome with 2 signals and the other with only one signal

Question 11

VCFS symtpoms

Answer 11

learning disabilities
short stature
cleft lip
facial anomolies
cardiac anomolies
feeding difficulty
weak immune system

Question 12

describe XY females

Answer 12

XY female - if individual genes that are essential for building strutures necessary for building final phenotype are not functioning. The genes don’t function, don’t get male strucures as expected.

EXAM Q - testicular feminization - inside of her are testicles. No good uterus. 46,XY woman - not a male because the male genes don’t get turned on. Obviously will not get menses.

• this is female with fertility problem, lacking receptor that responds to testosterone signal leading to wolferin ducts proliferation and mullerian ducts retreating.
• lots of testosterone signal, but the wulfian ducts don’t proliferate. The mullerian ducts proliferate.

Question 13

XX male

Answer 13

XX male
-gene on crucial Y can be translocated onto X chromosome during meiosis. You can contribute an X chromosome that has a Y determining factor on it.

Question 14

what happens when a person is identified to have a balanced translocation?

Answer 14

offer testing to all first degree relatives (parents, siblings, children) EXAM Q. it won’t hurt them, but their pregnancies may be at risk for adverse outcomes.

Question 15

gonadoblastoma

Answer 15

rare benign tumor that has the potential for malignant transformation and affects a subset of patients with an intersex disorder

Question 16

In human females, X-inactivation is a permanent change affecting all cells.

Answer 16

False, X-inactivation is permanent in the somatic cells, but all X chromosomes will become active in the germ cells during gametogenesis.

Question 17

After five miscarriages, karyotype analysis revealed that your patient, Sara, has a paracentric inversion of chromosome 8. She wants to understand what this means. Which of the following pieces of information is the most appropriate on which to base your counseling session?

Answer 17

A. Biologically, it is quite possible for Sara to have normal children, but she needs to be patient because the presence of the inversion may result in further miscarriages.

Paracentric inversion carriers may have difficulty getting pregnant and there may be an increased risk of spontaneous fetal loss, but they can have normal children, so there is no need to seek other options unless the parents wish to do so. For this type of inversion, chromosome imbalances are usually lost during gametogenesis, so the highest probability is that children will have a balanced genome and will be clinically normal with respect to the inversion. If the partner also has a chromosomal abnormality, that will complicate the issue further.

Question 18

A patient has a balanced translocation. The four chromosomes are designated: A1, derA (derived from a translocation B to A), B1, and derB (derived from a translocation A to B). Alternate segregation in meiosis will result in the following types of gametes:

A. A1 + B1, derA + derB

B. A1 + derB, B1 + derA

C. A1 + B1 + derB, derA

D. A1 + derA, B1 + derB

E. All of the above are possible

Answer 18

A. A1 + B1, derA + derB

Refer to the diagram of translocation in the handout. You will see that when both non-rearranged chromosomes separate together in one cell and both rearranged chromosomes separate together in the sister cell, that this is the pattern obtained for alternate segregation.

Question 19

An interstitial deletion is more likely to be deleterious than a terminal deletion. TF

Answer 19

False - The severity of a deletion is related to the size and which chromosome is involved.

Question 20

In mitosis in a human skin cell,

A. a diploid cell is reduced to the haploid state

B. replication of the DNA is followed by cell division resulting in daughter cells with a 2N complement.

C. at metaphase, two times the diploid number of chromosomes are present.

D. recombination of homologous alleles results in new haplotypes.

E. All of the above are true.

Answer 20

B. replication of the DNA is followed by cell division resulting in daughter cells with a 2N complement.

Only in germ cells, is the diploid complement reduced to haploid. At metaphase of mitosis, the diploid number of chromosomes is present. Recombination of homologous alleles occurs in meiosis. Hence, B is the correct answer.

Question 21

Reduction division:

A. occurs at anaphase of mitosis

B. occurs at metaphase of meiosis 2

C. reduces the DNA content from 2C to C

D. reduces the total number of chromosomes from 2N to N

E. is a key element in nondisjunction

Answer 21

D. reduces the total number of chromosomes from 2N to N.

meiosis

Question 22

A newborn with multiple congenital anomalies is seen in the neonatal intensive care unit. Karyotype analysis reveals that the baby has 46 chromosomes including a Robertsonian 15;21 translocation. What additional testing should be performed?

A. The diagnosis has been made, so no additional testing is necessary.

B. FISH should be performed to determine if a trisomy is present.

C. Molecular studies to determine the origin of the translocation.

D. Karyotype analysis of both parents to determine the risk for recurrence.

E. B, C, and D.

Answer 22

D - karyotype analysis of both parents to determine risk of recurrence

Based on the cytogenetic findings, you know the baby has trisomy 21. This is a definitive test, and you don’t need to do FISH to confirm it. However, since this is a structural rearrangement, it is possible that it was inherited from one of the parents. If this is the case, this couple could have another affected child in the next pregnancy. Therefore, it is indicated to check both parents’ chromosomes to determine if either is a carrier of a 15;21 translocation. It is not necessary to do molecular analysis to determine the parent of origin, since parent of origin is not the relevant question and the karyotype analysis will give you information that is much more specific and sensitive on the chromosomes.

Question 23

A man who has been diagnosed with X-linked red-green colorblindness marries a woman with normal vision and no family history of colorblindness. They have a son who is red-green colorblind. Which of the following could explain this situation?

A. A new mutation in the inherited maternal X.

B. An XXY male in which the only maternal X is inactivated in all cells.

C. A de novo X:autosome translocation in the son in which the breakpoint on the X chromosome disrupts the gene for red-green color vision.

D. A and B only

E. All of the above are possible

Answer 23

All three choices (A-C) are possible mechanisms that would result in an affected son. Some are more likely than others, but this was not the question.

Question 24

A baby is born with multiple congenital anomalies. By age 3, he clearly shows signs of developmental delay. Phenotypically, he appears very different than his siblings and parents. A family history shows three generations of multiple miscarriages in the father’s family. A paternal great-uncle was delayed and died early in life. What is the most likely cause of this child’s medical problems?

A. fragile X syndrome

B. a chromosome abnormality

C. a genetic syndrome in which developmental delay is a key feature

D. a point mutation in a gene associated with developmental delay

E. can’t tell from the information given

Answer 24

chromosome abnormality

the scenario described above is classic for a familial chromosome abnormality. The three generations of multiple miscarriages clinches the interpretation. Fragile X and developmental delay are not associated with miscarriage.

Question 25

XYY males and XXX females are similar in that they:

Answer 25

B. are usually fertile and phenotypically “normal”.

XXX females may arise as either maternal or paternal meiotic errors. Neither has been associated with increased aggression, and neither is usually infertile. B is correct.

Question 26

A female patient is referred for primary amenorrhea. A full clinical workup reveals no internal female genitalia, testes in the abdominal cavity, and a 46,XY karyotype. The most likely explanation for this is:

Answer 26

E. Mutation of the androgen receptor gene on the X chromosome resulting in complete lack of protein product.

As discussed in class, this describes an individual with an androgen receptor gene defect. Answer A would be similar to XYY. Answers B and C should have a female phenotype or, for C, possibly be inviable. Answer D is nonsense.

Question 27

what may cause XYY?

Answer 27

A karyotypically undetectable duplication of the short arm of the Y chromosome resulting in 2 copies of the TDF gene.