19.03.22 Origin and significance of markers Flashcards
1
Q
List 3 names for marker chromsomes
A
- Small supernumerary marker chromosome (sSMC)
- Extra structurally abnormal chromosome (ESAC)
- Accessory chromosomes
2
Q
Definition of a marker chromosome
A
Structurally abnormal chromosome that cannot be identified by conventional banding alone and is equal to or smaller in size than chromosome 20 of the same metaphase spread
- Those bigger than Chr 20 tend to be large enough to identify
- if they are identified, then they are called a derivative chr and not a marker
- Can be derived from any chr but majority come from an acrocentric chromosome
- Can produce a phenotype but more than half do not
- 50% are mosaic (more common in non-acrocentric sSMC)
- Can cause infertility (as they interfere with meiosis)
- 77% are de novo (75% of which have a phenotype)
- 23% are inherited (75% of which have no phenotype) - maternal transmission is twice as common than paternal, due to selection of sperm without sSMC
3
Q
3 ways a sSMC can appear
A
1) in addition to a normal karyotype (e.g. 47,XX,+mar)
2) in addition to a numerical abnormality (e.g. Turner syndrome or T21)
3) as part of a structurally abnormal but balanced karyotype (e.g. robertsonian translocation, t(11;22))
4
Q
Composition of an sSMC
A
- 70% derived from short arms and pericentromeric regions of acrocentric chromosomes
- Can be inverted duplication chromosomes, small supernumerary ring chromosomes, complex SMC (from unbalanced transmission of balanced rearrangement)
5
Q
How are markers formed?
A
- Can occur due to numerical error with subsequent partial trisomy rescue, monosomy rescue, or result from an unbalanced structural rearrangement
- Can be meiotic or mitotic
6
Q
How to marker chromosomes behave at meiosis?
A
- Probably form univalent rather than synapsing with chromosome it has been derived from
- Very small markers are prone to loss during cell division
- Familial sSMCs are normally maternally inherited
7
Q
Phenotype associated with marker chromosomes
A
- Phenotype can be normal to severely affected
- Phenotype influenced by:
1) size and origin of euchromatin present
2) Level of mosaicism
3) Presence/absence of UPD of sSMCs sister chromosome - There are common marker syndrome
- Unique markers need to be assessed individually for potential phenotype
- Normally small markers, with little euchromatin, have a low risk of causing a phenotype
- Large markers with euchromatin - high risk
- If inherited from a normal parent, likely to have no effect but level of mosaicsm and affected tissue types need to be taken into account
8
Q
Pallister-Killian syndrome
A
- isochromosome 12p (so you get tetrasomy 12p)
- Phenotype is severe MR, seizures, characteristic facial features and diaphragmatic hernia
- Detectable in fibroblast tissues, but rarely found in blood
- Almost all cases are mosaic
- Can get false negative results for prenatals (as high as 10% of cases due to varying levels of mosaicism)
9
Q
Isochromosome 18p syndrome
A
- get tetrasomy 18p
Phenotype is microcephaly, frontal bossing, strabismus, low set ears, small nose/mouth and MRI abnormalities - Very rare and is often fatal
10
Q
Emanuel syndrome
A
- derivative chromsome 22 that causes trisomy for 11q23-qter and 22q11-qter
- Arises from unbalanced 3:1 segregation of recurrent t(11;22)
- Carriers have 10% risk of having an unbalanced baby
- Phenotype is severe ID, miceocephaly, FTT, facial asymmetry, preauricular tags, cleft palate, micrognathia, and renal/heart defects
11
Q
Cat-eye syndrome
A
- inv dup(22)
- Get tetrasomy for 22p-q11.2 (can get variable breakpoints)
Phenotype is MR, iris coloboma, downslanting palpebral fissures, anorectal/cardiac/renal malformations - Phenotype can vary a lot, from mild to severe (not linked to size of marker from variable breakpoints)
12
Q
Idic(15) syndrome
A
- Inv dup(15)
- Get tetrasomy for 15p-(somewhere between q11 and q14) - due to variable breakpoints
- Phenotype is dev del, autism, epilepsy and minor physical defects
- Phenotype associated with presence of PWS/AS region and is more severe when marker is maternally in origin
- Phenotype normally only seen in 50% of cases but this can be variable
13
Q
X chromosome derived SMCs
A
- Ring form is the most common
- 46,X,+SMC is associated with a variant Turner syndrome (can also be in addition to a normal 46,XX or XY cell line)
- Phenotype depends on whether XIST is present or not
- If XIST is absent - more likely to get a phenotype as marker is not inactivated
14
Q
Y chromosome derived SMCs
A
- Normally idic/inv dup Y
1) 46,X,+SMC with absence of SRY = get Turner like phenotype but also increased risk of gonadoblastoma
2) 46,X,+SMC with SRY but loss of Yq = get male infertility - If SMC contains any Y material then there is a 30% risk of gonadal tumours
15
Q
UPD
A
- See UPD in 5-10% of SMC cases
- Normally due to partial monosomy rescue
- Recommended that if SMC is derived from a chromosome linked to UPD then this should be tested for (i.e. 6, 15, 7, 11 etc)
