1b. Structural abn

Question 1

What is the most common Robersonian translocation?

Answer 1

75% der(13;14)(q10;q10)
10% der(14;21)(q10;q10)

Question 2

What is the nomenclature for balanced Robertsonian carrier?

Answer 2

45,XX,der(14;21)(q10;q10)
rob(14;21)(q10;q10)

Note: 45

Question 3

In males, der(13;14) is associated with male infertility due to …….

Answer 3

oligospermia

Question 4

What are the causes of abnormal phenotype with balanced rearengments?

What is the recomendation?

Answer 4

• Submicroscopic deletion/duplication
  *15‐40% of postnatally ascertained cases with abnormal phenotype
• Interruption of critical gene
• Position effect (X‐autosome translocation)
• UPD, particularly with Robertsonian
• Other (including coincidence!)

Sequencing the breakpoints is recommended

Question 5

In pericentric inversion:

The larger the inversion, the greater chance of a cross-over occurring leading to …….. (larger/smaller) regions of imbalance, greater chance of viable abnormal offspring

Answer 5

smaller

Larger inversion > smaller imbalance > higher chance of normal offspring

Question 6

Two disorders, one paternal inversion

Father carries: a large pericentric inversion
inv(11)(p15.4q24.1)

If Child inherits a recombinant chromosome: rec(11)dup(11p)inv(11)(p15.4q24.1)pat BWS (duplication of critical region)
or
Terminal gain of ~4 Mb of 11p and terminal loss of ~11.7 Mb of 11q Jacobsen (11q24 del)

Answer 6

Question 7

Pericentric inversion: gives gammetes with deletion and duplication on the same chr

Paracentric inversion gives: 2 normal viable, 2 abnormal non viable (dicentric and acentric)

Question 8

What are the most common clinically significant marker chromosomes?

Answer 8

• Isodicentric 15q –when PWS/AS critical region is duplicated, maternal transmission is associated with autisms/seizures (Most common marker chromosome)
• Isodicentric 22q –Cat Eye syndrome
• Isochromosome 12p –Pallister Killian (not in T cells)

Question 9

A child born with multiple congenital anomalies is found to have a 4.5 Mb interstitial deletion in the q arm of chromosome 9 by chromosomal microarray. Which of the following parental balanced chromosomal rearrangements is the most likely cause of this unbalanced chromosomal complement in the offspring?

Answer 9

Balanced insertion

A balanced parental insertion can result is an offspring with either a balanced karyotype (normal karyotype and balanced insertion) or an unbalanced karyotype (interstitial deletion or duplication)

Question 10

A phenotypically normal individual is a carrier for a Robertsonian translocation between chromosomes 14 and 21. After adjacent segregation during meiosis I, which of the following possibilities is the most likely karyotypic outcome for this woman’s liveborn offspring?

Answer 10

Offspring with 1 copy of chromosome 14, 2 copies of chromosome 21 and a Robertsonian chromosome 14;21

In this 14;21 Robertsonian translocation example, adjacent segregation will produce 4 potential gametes. Monosomy of chromosome 14 and 21 are lethal, and trisomy of chromosome 14 is also lethal. The only viable possibility is trisomy 21 with 1 copy of chromosome 14, 2 copies of chromosome 21 and a Robertsonian chromosome 14;21