Marker Chromosomes at PND

Question 1

What are sSMC = small supernumerary marker chromosomes?

Answer 1

Morphologically heterogeneous group of structural abnormal chromosomes:inverted dups, minute chromosomes and rings can be detected.
cannot be identified unambiguously by conventional banding cytogenetics alone, and are equal in size or smaller than a chromosome 20 of the same metaphase spread.

Question 2

prevalence of markers in a prenatal setting

Answer 2

~1/1000

Question 3

Why is the significance of prenatally detected markers prone to ascertainment bias?

Answer 3

lack follow up in liveborn patients and cases resulting in termination will generally have major structural malformations

Question 4

Current best practice guidelines (Prenatal diagnosis 2009 v1.00 ) AGGS suggest what to investigate sSMC?

Answer 4

• C-banding to establish the presence/absence of C+ve heterochromatin and C-ve euchromatin.
• establish the number of centromeres-mono or dicentric
• Silver staining to establish presence of satellite structures -> narrowing down chromosome of origin to 13, 14, 15, 21, 22.

Question 5

80% of markers are derived from…

Answer 5

Chromosome 15

Question 6

For markers Parental blood samples should be requested as soon as possible, to:

Answer 6

investigate inheritance-less likely to be patho if inherited.
Extract DNA for possible UPD.

Question 7

For markers how should FISH testing should be performed?

Answer 7

sequential tests until marker origin is established

Question 8

what hampers FISH determinate of the origin of certain markers?

Answer 8

the centromere probes for ch 13 and 21 are the same as are ch 14 and 22. Therefore the origin can only be narrowed down to 1 of 2 chromosomes with these probes.

Question 9

UPD risk chromosomes are:

Answer 9

7, 11, 14, 15

Question 10

Two types of Chr15 marker are:

Answer 10

largely benign small inv dup(15)
larger pathogenic inv dup (15) containing SNRPN gene in the PWS/ AS- characterised by mental retardation, epilepsy and autism.

Question 11

Ch 22 markers require further tests to determine:

Answer 11

whether euchromatin is present and the involvement of the cat eye syndrome region.duplication/triplication of 22q11.2 likely to be supernumerary idic22q11.2

Question 12

UPD studies should be considered where

Answer 12

markers are derived form 7, 11, 14, 15

Question 13

For Sex Ch derived markers it is important to investigate the presence or absence of:

Answer 13

XIST

Question 14

array CGH to determine marker constitution however:

Answer 14

poor/no coverage in pericentromeric heterochromatin regions and satellite regions, lack of positional information and inability to detect low level mosaicism). There may also be issues with unexpected/incidental findings.
Depending on level of mosaicism (if any) and tissue distribution, the array may or may not detect a marker.