Discrepant cytogenetic, MLPA and array CGH results on a der(X)(pter->q27.2::p22.31->pter): the advan...
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M N Collinson, S Huang, JN Macpherson, VK Maloney, AC Skinner, A Karcanias, NA Affara, NS Thomas - PowerPoint PPT Presentation


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Discrepant cytogenetic, MLPA and array CGH results on a der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach. M N Collinson, S Huang, JN Macpherson, VK Maloney, AC Skinner, A Karcanias, NA Affara, NS Thomas. 30 year old female with premature ovarian failure (POF).

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Discrepant cytogenetic, MLPA and array CGH results on a der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach.

  • M N Collinson, S Huang, JN Macpherson, VK Maloney, AC Skinner, A Karcanias, NA Affara, NS Thomas


30 year old female with premature ovarian failure (POF) der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach.

molecular genetic testing

for a FRAXA premutation

cytogenetic analysis

only one allele found

?45,X or 46,XY

46,XX


MLPA with the Rett syndrome kit der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach.

MRC-Holland kit PO15C


LIST OF PROBES USED FOR FISH TO CONFIRM DELETION der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach.

Centromere

RP1-142F18 Normal (Xq27.2)

RP1-315J21 Deleted (Xq27.3)

RP11-79A21 Deleted (Xq27.3)

RP11-37P24 Deleted (fragile X locus)

RP11-161L9 Deleted (fragile X locus)

RP11-64L19 Deleted (Xq28)

RP11-533H4 Deleted (Xq28)

RP11-76K17 Deleted (Xq28)

RP11-402H20 Deleted (Xq28)

Telomere


FISH with a probe for the FRAXA gene der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach.

RP11-161L9

X centromere (control)


Blind cytogenetic analysis – 3 control slides and der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach.3 slides from POF patient scored by 3 independent analysts


Partial karyotype of the X chromosomes der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach.

(abnormal X on the right)


MLPA with the subtelomere probe kit der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach.

MRC-Holland kit PO36B


FISH with the Xp and Xq subtelomere probes der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach.

CY29 (Xp subtelomere)

c8.1/2 (Xq subtelomere)


Array-CGH der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach.

Agilent 244K oligoarray


FISH with SHOX probe der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach.

RP11-946P8

DXZ2 (X centromere control)


MLPA with SHOX kit PO18B der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach.

Duplication of SHOX

POF case


NORMAL CASE der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach.

FEMALE CONTROL

MALE CONTROL

Array CGH with chip specifically designed for

sex chromosome abnormalities


POF CASE der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach.

FEMALE CONTROL

MALE CONTROL

Array CGH with chip specifically designed for

sex chromosome abnormalities


L.M. Russell et al, Cytogenet Genome Res 116:181-185 (2007) der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach.


Original cytogenetic analysis – 1/30 metaphases 45,X der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach.

Blind FISH study with X centromere probe (DXZ2)

POF case

Control

Metaphases

1/30 45,X (3.3%)

1/30 45,X (3.3%)

Interphase cells

8/100 45,X (8%)

6/100 45,X (6%)


Summary
Summary der(X)(pter->q27.2::p22.31->pter): the advantages of an integrated approach.

  • An integrated approach was required to establish the true nature of the X chromosome abnormality

  • Highlights the fact that one should be cautious of any shifts from the baseline when analysing array CGH as it may mask significant changes in log ratios

  • We still do not have a satisfactory explanation of our results other than mosaicism

  • Deletions of this region of Xq have been reported in association with POF


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