Severe microcephalyGene: ATP11A
Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is currently only 1 case and a mouse model which showed neurological deficit phenotypes (including tremors, abnormal gait, hind limb clasping and reduction in brain size. The patient was a 26 yo male born to healthy non-consanguineous Japanese parents. At birth his length was -3.3. SD and OFC was -1.3 SD. Developed epilepsy at 2 weeks followed by global developmental delay and mild hypothyroidism and cataracts.He suffered gradual lost of developmental milestones. At 18 yo, height was -4.6 SD and OFC was -4.0 SD.
As the mouse model did not show signs of microcephaly, there is currently not enough evidence to support a gene-disease association, this gene has been given an Red rating.
Created: 13 Oct 2021, 12:10 p.m. | Last Modified: 13 Oct 2021, 12:12 p.m.
Panel Version: 2.259
- Single de novo missense variant reported in a patient with developmental delay and neurological deterioration.
- Patient MRI showed severe cerebral atrophy, ventriculomegaly, hypomyelination leukodystrophy, thinned corpus callosum. Axonal neuropathy suggested.
- K/I heterozygous mice died perinatally.
- Functional studies on missense variant show plasma membrane lipid content impairment, reduced ATPase activity etc.
gnomAD: some NMD PTCs present, good quality variants found with 4-5 hets.
Created: 11 Oct 2021, 9:24 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gene: atp11a has been classified as Red List (Low Evidence).
gene: ATP11A was added gene: ATP11A was added to Severe microcephaly. Sources: Expert Review Amber,Literature watchlist tags were added to gene: ATP11A. Mode of inheritance for gene: ATP11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP11A were set to 34403372 Phenotypes for gene: ATP11A were set to Neurodevelopmental disorder