Mosaicism

Question 1

What is somatic mosaicism

Answer 1

Mosaicism that only occurs in the body (soma) so can’t be passed on
earlier in embryogenesis it occurs the higher the fraction cells affected

Question 2

What’s segmental mosaicism

Answer 2

Where some body parts have abnormality and display the phenotype and some ares don’t

Question 3

What’s is germline mosaicism

Answer 3

Usually not detected until the person has had to affected children by and apparently de novo abnormality
Only occurs in the gonads
Arises during the formation of the gonads (~30mitotic divisions prior to meiosis where this could occur)

Question 4

What’s somatic gonadal mosaicism

Answer 4

Both soma and germline cells involved

Question 5

What’s dynamic mosaicism

Answer 5

Description of mosaicism for rings

At cell division rings are broken/ doubled/ entangled results in different ring structure in diff cells

Question 6

What 2 types of mosaicism are seen in fragile X syndrome

Answer 6

Mutational (diff sized expansions due to somatic instability of the repeat) ~ 20% males
Methylation (same sized expansion in all cells but with varying methylation patterns)

Question 7

What is confined placental mosaicism

Answer 7

An abnormal cell line is present only in the placenta and not the foetus. Usually because of an event later on once fetal and extraembryonic lineages had diverged.
Present in CVS, not in AF

Question 8

What are the two ways mosaicism can occur

Answer 8

Postzygotic Mitotic NDJ (majority of cases)

Trisomy rescue

Question 9

Describe postzygotic Mitotic NDJ

Answer 9

Non disjunction occurs postzygotically resulting in a normal, trisomic and monosomy cell line.
The monosomy cell line will die out due to growth deficiency leaving the normal and the trisomic cell line

Question 10

Describe trisomy rescue

Answer 10

Anaphase lag of a trisomic conceptus
Loss by delayed movement of the additional chromosome
Either by failure to attach to the spindle or by moving slowly-
Results in it not being incorporated into the Newley forming daughter cell, forming a micronucleus and being lost

Question 11

Which mosaicism are associated with trisomy rescue

Answer 11

mT13
mT21
mT18
45,XO

Question 12

Which mosaicism is associated with postzygotic NDJ

Answer 12

mT8

Question 13

What is hypomelanosis of Ito

Answer 13

Heterogeneous group of disorders characterised by HYPOpigmentated skin and streaks that follow the Blaskhos lines with neurological defect, epilepsy, asymmetrical abns of organs

Question 14

What disorders are associated with Hypomelanosis of Ito

Answer 14

Polyploidy
Anueploidy
Del/ ins/t

Question 15

What’s a correcting event

Answer 15

Mosaicism in lymphocytes of affected patients whereby spontaneous reversion to the wt state is observed
Resulting a a false positive result
Only occurs in lymphocytes (lymphoid precursor)

Question 16

What disorders are associated with correcting events

Answer 16

Fanconi anaemia: 25% pts

Bloom’s syndrome: 20%pts

Question 17

What is age related mosaicism

Answer 17

Women lose an X with age

Men loose Y with age

Question 18

What is considered significant loss of X in a blood sample

Answer 18

99th centime on a 30 cell count:

30yrs: 6%
40yrs: 9%
50yrs: 13%
60yrs: 17%

Question 19

What disease are associated with loss of Y in bone marrow

Answer 19

MDS, MPD, AML, LPD

Question 20

Name some tissue specific mosaicism disorders

Answer 20

Pallister Killian: +i(12p) seen in fibroblasts (cultured out of blood)
mT20: abn cells in renal and genitourinary tract/ buccal epithelial cells/ fibroblasts
mT8: better tolerated in fibroblasts

Question 21

Name some monogenic disorders associated with mosaicism

Answer 21

Neurofibromatosis 1: somatic gonadal mosaicism for germline mutation/ occasional segmental mosaicism
mcCune-Albright syndrome: GNAS: SOMATIC MOSAICISM not inherited
Osteogenesis Imperfecta type 2: COL1A1/ COL1A2: GERMLINE MOSAIC PARENT

Question 22

Name the 3 types of mosaicism

Answer 22

Somatic
Germline
Somatic gonadal

Question 23

What counts are required to exclude mosaicism at 10%

Answer 23

90% confidence: 22 cells
95% confidence: 29 cells
99% confidence: 44 cells

Question 24

What counts are required to exclude mosaicism at 5%

Answer 24

90% confidence: 45 cells
95% confidence: 59 cells
99% confidence: 90 cells

Question 25

Describe briefly mitochondrial mosaicism

Answer 25

at cell division the mitochondria segregate randomly
They also have a high mutation rate
So mosaicism is both # in cells and mutations within those mitochondria

Question 26

What’s considered normal loss of the X chromosome in cultured blood samples for females.

Answer 26

Thirty years it’s less than 1 %. Forty years it’s 2%, at fifty years it’s 3%, at sixty five years it’s 5%