Severe microcephaly

Gene: ATP1A2

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 10 Mar 2022, 10:52 a.m. | Last Modified: 10 Mar 2022, 10:52 a.m.

Panel Version: 2.282

Comment on list classification: New gene added by Zornitza Stark. At least 4 unrelated families with multiple congenital abnormalities and different homozygous truncating variants in the ATP1A2 gene. All were affected by microcephaly, and where measurements were specified, the severity was within the scope of this panel.

Rating Amber but there is sufficient evidence to promote to Green at the next GMS panel update (added 'for-review' tag)

Created: 18 Jan 2021, 11:53 a.m. | Last Modified: 18 Jan 2021, 11:53 a.m.

Panel Version: 2.70

Green List (high evidence)

This is a distinct phenotype from the one associated with mono-allelic variants.

PMID: 30690204;
- 2 families with severe microcephaly (-6 to -8 SD)
- both homozygous PTVs

PMID: 31608932;
- 4 patients from 2 families
- Family A, all 3 affecteds had severe microcephaly during ultrasound (-3 to -4 SD)
- Family B, no measurements were reported
- both homozygous PTVs
Sources: Expert list

Created: 31 Aug 2020, 11:10 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
hydrops fetalis, microcephaly, arthrogryposis and extensive cortical malformations

Publications

• 30690204
• 31608932

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