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

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M n collinson s huang jn macpherson vk maloney ac skinner a karcanias na affara ns thomas

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


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)

molecular genetic testing

for a FRAXA premutation

cytogenetic analysis

only one allele found

?45,X or 46,XY

46,XX


M n collinson s huang jn macpherson vk maloney ac skinner a karcanias na affara ns thomas

MLPA with the Rett syndrome kit

MRC-Holland kit PO15C


M n collinson s huang jn macpherson vk maloney ac skinner a karcanias na affara ns thomas

LIST OF PROBES USED FOR FISH TO CONFIRM DELETION

Centromere

RP1-142F18Normal (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


M n collinson s huang jn macpherson vk maloney ac skinner a karcanias na affara ns thomas

FISH with a probe for the FRAXA gene

RP11-161L9

X centromere (control)


M n collinson s huang jn macpherson vk maloney ac skinner a karcanias na affara ns thomas

Blind cytogenetic analysis – 3 control slides and 3 slides from POF patient scored by 3 independent analysts


M n collinson s huang jn macpherson vk maloney ac skinner a karcanias na affara ns thomas

Partial karyotype of the X chromosomes

(abnormal X on the right)


M n collinson s huang jn macpherson vk maloney ac skinner a karcanias na affara ns thomas

MLPA with the subtelomere probe kit

MRC-Holland kit PO36B


M n collinson s huang jn macpherson vk maloney ac skinner a karcanias na affara ns thomas

FISH with the Xp and Xq subtelomere probes

CY29 (Xp subtelomere)

c8.1/2 (Xq subtelomere)


M n collinson s huang jn macpherson vk maloney ac skinner a karcanias na affara ns thomas

Array-CGH

Agilent 244K oligoarray


M n collinson s huang jn macpherson vk maloney ac skinner a karcanias na affara ns thomas

FISH with SHOX probe

RP11-946P8

DXZ2 (X centromere control)


M n collinson s huang jn macpherson vk maloney ac skinner a karcanias na affara ns thomas

MLPA with SHOX kit PO18B

Duplication of SHOX

POF case


M n collinson s huang jn macpherson vk maloney ac skinner a karcanias na affara ns thomas

NORMAL CASE

FEMALE CONTROL

MALE CONTROL

Array CGH with chip specifically designed for

sex chromosome abnormalities


M n collinson s huang jn macpherson vk maloney ac skinner a karcanias na affara ns thomas

POF CASE

FEMALE CONTROL

MALE CONTROL

Array CGH with chip specifically designed for

sex chromosome abnormalities


M n collinson s huang jn macpherson vk maloney ac skinner a karcanias na affara ns thomas

L.M. Russell et al, Cytogenet Genome Res 116:181-185 (2007)


M n collinson s huang jn macpherson vk maloney ac skinner a karcanias na affara ns thomas

Original cytogenetic analysis – 1/30 metaphases 45,X

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

  • 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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