Cytopenias and congenital anaemias

Gene: ATRX

I don't know

Comment when marking as ready: Discussed with Richard Scott. Agrees that gene should not be green in view of lack of evidence for isolated haematological findings in affected males, this is therefore an unlikely route for recruitment as cases will be picked up via the ID panel for example instead. If evidence emerges of haematological anomalies in the absence of the other (ID, dysmorphism) aspects of the syndrome then re-consider.

Created: 2 Mar 2017, 9:23 p.m.

Comment on phenotypes: Only somatic mutations identified as a cause of isolated haematological presentation to date

Created: 2 Mar 2017, 9:21 p.m.

I can only find an isolated haematological phenotype in somatic mutations. The clinical presentation (and therefore entry into the project) is unlikely to be via haematological route, given the more severe clinical features in affected males (ID, dysmorphism). Therefore I would be concerned about interpreting variants in boys with isolated haematological findings as I don’t think there is an evidence base for this in the current literature. Therefore, consider as amber, even though there is an associated phenotype, unless evidence emerges of an isolated haematological presentation.

Created: 2 Mar 2017, 9:17 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Alpha-thalassemia myelodysplasia syndrome, somatic 300448; Alpha-thalassemia/mental retardation syndrome 301040 XLD

Comment on mode of inheritance: Gene2Phenotype indicates "hemizygous" for both ALPHA-THALASSEMIA MENTAL RETARDATION SYNDROME X-LINKED NON-DELETION TYPE and MENTAL RETARDATION SYNDROMIC X-LINKED WITH HYPOTONIC FACIES SYNDROME TYPE 1. From the publsihed reports, female carriers in general seem to have marked skewing of the X chromosome favouring inactivation of the mutated allele. There is however a case where a heterozygous girl is affected: PMID: 16955409.

Created: 23 Feb 2017, 2:14 p.m.

Comment on list classification: This is a confirmed DD gene for ALPHA-THALASSEMIA MENTAL RETARDATION SYNDROME X-LINKED NON-DELETION TYPE (includes Hypochromic microcytic anemia,
Reduced alpha/beta synthesis ratio) and MENTAL RETARDATION SYNDROMIC X-LINKED WITH HYPOTONIC FACIES SYNDROME TYPE 1 (includes Abnormality of blood and blood-forming tissues) in Gene2Phenotype, and multiple cases/families reported for Alpha-thalassemia/mental retardation syndrome 301040 in OMIM. Somatic variants in this gene have also been reported in patients with alpha-thalassemia myelodysplasia syndrome (PMID: 12858175).

Created: 23 Feb 2017, 2:03 p.m.

Green List (high evidence)

Mode of inheritance
Unknown

Phenotypes
Myelodysplastic syndrome (MDS), Adult

Variants in this GENE are reported as part of current diagnostic practice