Clinical cytogenetics

Question 1

ALL

Answer 1

Childhood B-cell acute lymphoblastic leukemia.

High hyper-diploidy revealed by chromosome and FISH analyses. Associated with FAVORABLE prognosis.

Question 2

CML

Answer 2

t(9;22), chronic myelogenous leukemia, treated with TKI’s or gleevec.

Question 3

APML

Answer 3

acute promyeloid leukemia. t(15;17). Treated with retinoic acid.

Question 4

FISH probes

Answer 4

Used for initial differential dx. And a way to monitor treatments or disease progression.
Can see # of a chromosome or translocation.
Specific, cloned DNA sequences.
Short list of fluorescent-labelled probes (centromere- enumeration leukemias. Locus specific- deletion leukemias. Fusion or dual fusion- translocation leukemia).

Question 5

SNP based CMA

Answer 5

Synthetic oligomers put onto a ‘platform’ (bead chip)… highly quality controlled.

Question 6

CMA methods

Answer 6

Take blood, amplify and label DNA (with synthetic DNA oligomers), compare to intensities of other people’s blood DNA. Pt’s is labelled with green, reference is red.
Can show deletions or duplications.

Question 7

CNV’s

Answer 7

Important to know that the population has duplications/deletions for which no phenotype exists.

Important resource is thus the Database of Genomic Variants (DGV)…
each normal indiv has 10-20 CNV’s.

Question 8

Testing for kids with autism, cognitive disability, developmental delays etc.

Answer 8

If detect deletion/duplication with CMA, consult DGV
Parental FISH studies to see if finding is rare, normal, familial variant
Deletion/duplication found on parents, can test other family.
If not found on parent or DGV, do further data and literature searching. Often you will find syndromic association.