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Microarray
Developed by Dr. Judith Allanson, Ms. Shawna Morrison and Dr. June Carroll
*for ethnicity-based
screening, if both
If negative members of the couple
If positive*
or decline are carriers of the same
condition
Indication
Advanced maternal age, multiple soft markers on ultrasound, ultrasound anomaly,
positive prenatal screen, etc.
Additional Testing
No further testing
e.g. Chromosomal
microarray
What is chromosomal microarray (CMA)?
1. Normal
2. Pathogenic
3. Variant of Uncertain Significance (VUS)
4. Incidental Finding
What do the genetic test results mean?
Normal: No clinically significant copy number changes were
identified in the DNA of this specimen in the areas tested
Variant of
Unknown
significance 4,164 other 1.1% had clinically
(VUS) are found indications1 significant CNV (44/4,164)
in about 1% of
cases2,3
McDonald-McGinn, 2015
22q11.2 deletion syndrome
• Multi-system disorder with variable expressivity
– Clinical presentation will vary between affected individuals even within the
same family (variable expressivity)
• Features include:
McDonald-McGinn, 2015
Back to case 2
• 42-year-old G3P2 woman
• No significant family history or history of
prenatal exposure
• Integrated Prenatal Screening (IPS) was
positive
– 1 in 100 versus her age-related risk to have a baby
with Down syndrome of about 1 in 61
Back to case 2
• Patient chose amniocentesis
• QF-PCR showed normal female
• This genetics centre has implemented a new
algorithm for all prenatal invasive testing so that
all normal QF-PCR samples are then sent for
chromosomal microarray testing
• Chromosomal microarray results showed a
pathogenic deletion that includes the BRCA1
gene
Back to case 2
• This incidental finding has diagnosed the fetus with
an adult-onset hereditary cancer predisposition
syndrome
• Consider:
– Was disclosure of incidental results, including adult onset
conditions, part of the pre-test counselling and consent?
– Implications for autonomy and insurance discrimination
for the fetus
– Implications if either parent carries this deletion and is at
increased risk for cancer
Prenatal Microarray
• Chromosomal microarray (CMA) has a greater
yield than traditional karyotype, particularly in
high risk pregnancies
• There is variability in practice with regards to
who will be offered prenatal CMA
• Consent, pre- and post- test counselling is
complicated
Resources
• Visit www.geneticseducation.ca to connect to your local genetics centre and
for the GECKO on the run resource
• You may also wish to consult your local maternal-fetal medicine (MFM)
specialist or high risk obstetrician/gynaecologist depending on the reason
CMA has being considered
• If there are terms that require further elaboration please visit the GECKO
Glossary in Educational Resources
• Unique – Disorder Guides
– Unique has been collecting information about specific chromosome disorders in
their offline database for nearly 30 years and produces family-friendly,
medically-verified, disorder-specific information guides.
• Orphanet
– A reference portal for information on rare diseases and orphan drugs, for all
audiences
How to explain genetic testing to
patients
Library analogy for explaining genetic
testing
• Clinical examination =
• Observing the outside
of building
– Number of windows
– Doors
– Roof
– Height of the windows
Wikimedia
Library analogy for explaining genetic
testing
• Karyotype =
• Standing in one spot in the
library and looking at the
number of rows (46 rows, 2
row 1s, 2 row 2, etc… the
location of the rows, large
extra or missing pieces
Wikimedia
Library analogy for explaining genetic
testing
• Microarray =
• Walking through the library
and seeing if there are
extra or missing shelves
• A shelf may be thought of
as a collection of books or
genes, that are closely
located and extra or
missing shelves would be
called microduplication or
microdeletions
Flikr.com
Library analogy for explaining genetic
testing
• Sequencing
– Next-gen sequencing, Sanger
sequencing
=
• Reading through the books
word by word, letter by
letter to detect small
changes: substitutions,
extra or missing words
Wikimedia.org
www.2dayfm.com.au