Variable Expression of Lung Disease Due to a Novel Homozygous Variant.

Mutations in the ATP-binding cassette transporter A3 () gene are one of the most common surfactant disorders leading to interstitial lung diseases (ILD). The clinical spectrum and severity of lung disease caused by ABCA3 deficiency due to missense variants is variable. A novel c.3135G>C (p.Gln1045His) mutation was identified at the homozygous state in 3 subjects from 2 unrelated families: one 19-month-old boy with severe ILD and his homozygous pauci-symptomatic mother, and one 10-year-old girl with moderate late-onset ILD. Corticosteroid pulses associated with hydroxychloroquine were beneficial for both children. We illustrate here the huge intra- and interfamilial phenotypic variability associated with the same homozygous missense mutation, and the benefit of identifying the disease for treatment, follow-up, and appropriate genetic counseling.