Cytogenetics And Learning Disorders Part 3

Question 1

What can segregation of a balanced reciprocal translocation result in?

Answer 1

• normal/balanced products (alternate segregation)
• unbalanced products as a result of 2:2 (adjacent) segregation
• unbalanced products as a result of 3:1 (tertiary or interchange) segregation

Question 2

Name the only viable segregation product arising from the recurrent translocation t(11;22)(q23;q11)

What syndrome does it cause?

Answer 2

• Tertiary trisomy: gain of 22pter-22q11 and 11q23-11qter
• results in Emanuel syndrome: 47, XX, +der(22)t(11;22)
• clinical features include mental retardation, craniofacial abnormalities and congenital heart defects

Question 3

Name the two viable segregation products arising from the recurrent translocation t(4;8)(p16;p23)

Answer 3

Both are adjacent 1 segregants

• 46, XX, der(4)t(4;8) results in a Wolf Hirschhorn phenotype
• 46, XX, der(8)t(4;8) is associated with less specific features

Question 4

What are the two main types of insertional translocation?

Answer 4

1. Interchromosomal: where a segment from one chromosome is inserted into a different chromosome
2. Intrachromosomal: where a segment from one chromosome is inserted into a different place within the same chromosome

Question 5

How do insertional translocations differ from reciprocal translocations?

Answer 5

They are three breakpoint translocations whereas reciprocal translocations only have two breakpoints

Question 6

What are the reproductive risks involved with insertional translocations?

Answer 6

• Depends on the size and gene content of the inserted segment
• generally the risk for an insertion carrier is higher than for a translocation carrier because the unbalanced form consists of either a gain or loss, not a compound of both

Question 7

What is a ring chromosome and what are the two main types?

Answer 7

A ring chromosome is formed from a single chromosome with loss of material from and then fusion of the p and q arms. You can either have:

• large ring chromosomes with little material deleted in place of the normal chromosome e.g. 46, XX, r(4)
• additional ring chromosomes, often small supernumerary markers e.g. 47, XX, +r

Question 8

Describe the behaviour of ring chromosomes

Answer 8

Subject to frequent errors at mitotic division resulting in dynamic mosaicism, which can result in cells with:

• loss of the ring
• additional copies of the ring
• double size rings

Question 9

What is generalised ring chromosome syndrome?

Answer 9

• associated with large rings replacing a normal homologue
• growth restriction/short stature with or without learning disability resulting from the associated dynamic mosaicism
• other clinical features dependent on the size and genetic content of the deleted segments

Question 10

What are the four main categories of combined imbalance with regards to cytogenetic abnormality?

Answer 10

• segregation of translocations
• recombination of inversions
• segregation of insertional translocations
• ring chromosomes