Hypomorphic pathogenic variant in SFTPB leads to adult pulmonary fibrosis.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
12
12
2022
accepted:
12
06
2023
revised:
25
05
2023
pmc-release:
01
09
2024
medline:
4
9
2023
pubmed:
29
6
2023
entrez:
28
6
2023
Statut:
ppublish
Résumé
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 SFTPB pathogenic variant, c.582G>A p.(Gln194=). In vitro transcript studies showed that this SFTPB synonymous pathogenic variant induces aberrant splicing leading to three abnormal transcripts with the preservation of the expression of a small proportion of normal SFTPB transcripts. 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 SFTPB pathogenic variants should be considered in atypical presentations and/or early-onset forms of ILD particularly when a family history is identified.
Identifiants
pubmed: 37380697
doi: 10.1038/s41431-023-01413-w
pii: 10.1038/s41431-023-01413-w
pmc: PMC10474257
doi:
Substances chimiques
Pulmonary Surfactant-Associated Protein B
0
SFTPB protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1083-1087Informations de copyright
© 2023. The Author(s), under exclusive licence to European Society of Human Genetics.
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