Protocol for ATR-X testing

We are very happy to help investigate any child suspected of having ATR-X syndrome. We provide diagnostic and molecular testing on a research basis that is not charged. If and when a mutation is identified then we provide a service for testing females etc for which we do make a modest charge.

Before proceeding with mutational analysis of the ATRX gene we employ 2 screening tests to confirm the diagnosis:

  1. Checking for HbH inclusions which are a feature of alpha thalassemia seen in the majority (85% of cases in which we have identified a mutation). If present then the diagnosis is very likely correct (although occasionally the thalassemia may be due to an independent thalassemia determinant which would be present in the parents).
  2. Checking for abnormalities in the pattern of methylation at a locus which is characteristic of patients with ATRX mutations. We believe the sensitivity of this test is ~75%.

Sample requirement

>10mls of fresh venous blood in EDTA anticoagulant. (For young children please contact us to discuss sample size).

This is used for haematological analysis, DNA extraction and where appropriate for establishing a lymphoblastoid cell line to facilitate mutation detection (we use RNA rather than DNA for efficient mutation analysis).

Blood should be sent by courier (and in summer sent in a cool box) for, if possible, next day delivery. The fresher the blood the more sensitive the HbH inclusion test. The sample should only be sent at the beginning of the week so as not to be delayed by the weekend.

Please also send photos and the following details of the affected individuals:

Reporting time

If the HbH inclusion test is positive then this would confirm the diagnosis - this would be reported in 2-3 days. We would then proceed with mutation analysis.

Methylation Pattern

If the HbH inclusion test is negative then it would take us 2 to 3 months to check the methylation pattern. If consistent with ATRX we would proceed to mutation analysis.

For the mutation analysis, we work our way through the gene starting in the regions most commonly affected. Overall we detect 85-90% of mutations but it may take weeks if we are lucky or >12 months if the mutation is not in a commonly affected region.