An unusual case of mosaicism for two structural rearrangements of chromosome 12 in a phenotypically

1
An unusual case of mosaicism for two
structural rearrangements of chromosome 12 in a
phenotypically normal male

• G.Forsyth, J.Cunningham, G.Hislop, L.McMahon,
• D.Goudie, and N.Pratt

2
Referral

• Male
• 2yrs old
• Developmental delay
• Large head

3
(No Transcript)
4
46,XY,inv(3)(q23q29),ins(1212)(p11.2?)
5
FISH

• WCP12 proved that extra material was derived from
  chromosome 12
• ? which part of 12
• Array CGH initiated and parental blood samples
  requested

6
Array CGH

• BlueGnome CytoChip (version 2) 0.5Mb
• Data analysis with BlueFuse software (version 3.5
  (6446))

7
Array CGH

• Amplification of two regions of 12p
• 4 consecutive BAC clones from 12p12.3 measuring
  3.9Mb
• 7 consecutive BAC clones in the region 12p11.22
  to 12p12.1 measuring 5.1Mb
• 12p12.1 to 12p12.3 showed a normal pattern

8
BAC FISH

• Confirmed amplified regions
• Triplicated

RP11-250G2
RP11-69M1
9
Tetrasomy 12p

• MR
• Seizures
• Abnormal facial features-
• -prominent forehead
• -sparse anterior scalp hair
• -hypertelorism
• Streaks of hypo/hyper pigmentation

10
Parental Results

• Maternal 46,XX,inv(3)(q23q29)
• - normal phenotype
• - no imbalance on array of proband at
  chromosome 3
• - not clinically significant
• Paternalmosaicism for two abnormal cell lines
• - normal phenotype

11
Karyotype result-gain of 12p 50
12
Karyotype result-loss of 12p50
13
Array CGH

• Confirmed amplified regions as identical to those
  seen in the proband
• The more proximal region showed a lower level of
  gain with the intervening region also skewed
  towards a loss
• Deletion of 8Mb from 12p12.3 to 12p11.22

14
(No Transcript)
15
BAC FISH
16
Array Comparison
father
proband
17
Skin fibroblasts

• DNA extracted from 2 separate cultures
• 70 cells contained triplicated 12p
• Remainder contained deleted 12p
• No normal cells found
• Array CGH confirmed the presence of the same
  abnormalities as seen previously
• Confirmed with BAC FISH

18
Summary

• Two abnormal cell lines
• No normal cells found
• Learning difficulties at school but otherwise
  normal phenotype
• Parental karyotypes apparently normal

19
Further Studies

• Research basis
• Orientation of additional material
• Possible mecahnisms
• Suggestions welcome!

20
Acknowledgements

• Joan Cunningham
• Gordon Hislop
• Lesley McMahon
• David Goudie
• Norman Pratt