Cardiomyopathy_Paediatric

Gene: ATAD3A

Green List (high evidence)

Mode of pathogenicity includes:
i) bi-allelic missense and nonsense variants and bi-allelic deletions that create an ATAD3B/ATAD3A fusion gene under the lowly expressed ATAD3B promoter (loss of function)
ii) monoallelic dominant-negative missense variants (either de novo or inherited) and de novo monoallelic duplications creating a ATAD3A/ATAD3C fusion gene (dominant negative)

The de novo monoallelic duplication form creating a dominant negative ATAD3A/ATAD3C fusion gene has a very characteristic phenotype of perinatal fatal cardiomyopathy, lactic acidosis, frequently associated with corneal clouding or cataracts, encephalopathy and 3-methylglutaconic acuduria. The Frazier et al paper from MCRI reports 17 cases for 16 families (1 family with affected identical twins), all de novo.

Created: 7 Nov 2020, 4:29 a.m. | Last Modified: 7 Nov 2020, 4:29 a.m.

Panel Version: 0.38

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Harel-Yoon syndrome, MIM# 617183; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (PHRINL SYNDROME), MIM# 618810; perinatal cardiomyopathy; cataracts; corneal clouding

Publications

• PMID: 32004445
• PMID: 27640307
• PMID: 28549128
• also Frazier et al, Med (in press)

Mode of pathogenicity
Other