Molecular Characteristics
ABCA2 encodes for the second member of the ATP-binding cassette subfamily A. The gene is highly expressed in the brain, with lower levels of expression present in most other tissues of the body, including the lungs, kidneys, heart, and muscles. The encoded protein is proposed to influence cholesterol regulation and LDL receptor expression, and may be involved in protection against reactive oxygen species.
Mutations and pathophysiology
Mouse knockout models for ABCA2 showed accumulation of gangliosides, cerebrosides, and sulfatides along with reduced sphingomyelin in the brain, although no gross abnormalities in cytoarchitecture was seen. The mice also displayed lower body weight, sensitization to environmental stress, and higher death rate. Pathogenic ABCA2 variants in humans lead to Intellectual Developmental Disorder with Poor Growth and with or without Seizures or Ataxia (IDPOGSA).
Maddirevula et al. (2019) reported two homozygous truncating variants in ABCA2 (NM_ 212533.2):
1) c.740dupT:p.[Gly248Argfs*38]) in a 13-year-old girl with IDPOGSA, without ataxia
2) c.1027C>T:p.[Gln343*]) in a 10 year-old boy with IDPOGSA, without ataxia
Hu et al. (2019) reported on 3 siblings born of consanguineous Iranian parents with ABCA2 mutation (c.4537_4547delinsG, predicted to result in Arg1513AlafsTer15). The patients had IDPOGSA, with variable ataxia.
ABCA2