Search

Biallelic pathogenic variants in the surfactant protein (SP)-B gene (SFTPB) have been associated with fatal forms of interstitial lung diseases (ILD) in newborns and exceptional survival in young children. We herein report the cases of two related adults with pulmonary fibrosis due to a new homozygous SFTPBpathogenic variant, c.582G>A p.(Gln194=). In vitro transcript studies showed that this SFTPBsynonymous pathogenic variant induces aberrant splicing leading to three abnormal transcripts with the preservation of the expression of a small proportion of normal SFTPBtranscripts. Immunostainings on lung biopsies of the proband showed an almost complete loss of SP-B expression. This hypomorphic splice variant has thus probably allowed the patients’ survival to adulthood while inducing an epithelial cell dysfunction leading to ILD. Altogether, this report shows that SFTPBpathogenic variants should be considered in atypical presentations and/or early-onset forms of ILD particularly when a family history is identified.