Aquarius^® Microdeletion Syndrome probes

Angelman (UBE3A/D15S10) Probe LPU006 - Detail

In 70% of patients with Prader-Willi or Angelman syndrome (AS) a large interstitial deletion of 3-4 Mb at 15q11-13 is observed^{1, 2}. Mutations of the imprinting centre and uniparental disomy account for the remaining cases of PWS. However, 20% of AS show biparental inheritance and normal methylation suggesting the involvement of a single AS gene.

The UBE3A gene lies within the minimum AS critical region³ approximately 400 kb telomeric of SNRPN, it shows preferential expression of the maternal allele in the brain⁴ and is mutated in 20-30% of AS patients with normal methylation and biparental contribution of 15q11-13. It is considered to be one of the AS genes⁴.

The Angelman Region probe is approximately 120 kb of genomic DNA and targets most of the UBE3A gene and includes the locus D15S10. It is designed for fluorescence in situ hybridisation to interphase cells and metaphase chromosomes from fixed cultured peripheral blood cells. The accompanying subtelomere specific probe at 15qter (clone 154P1) acts as a control probe.

The probe is intended to detect deletions of the AS region. It will not detect intragenic deletions or single mutation events. The probe may also be used to help determine the nature of a Prader-Willi syndrome deletion detected with the SNRPN/Imprinting Centre probe. Large deletions of 3-4 Mb at 15q11-13 will cause the deletion of both probe regions SNRPN/IC and UBE3A/D15S10. However, small deletions incorporating the IC and SNRPN, of approx. 200 Kb, will not cause deletion of the UBE3A/D15S10 probe. Such deletions may indicate a much higher risk of recurrence and patients could be referred for further investigation⁵.