SERPINA11 related novel serpinopathy - A perinatal lethal disorder.
Clin Genet
; 106(3): 367-373, 2024 Sep.
Article
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| MEDLINE
| ID: mdl-38831697
ABSTRACT
SERPINA11 is a hitherto poorly characterised gene belonging to Clade A of the SERPIN superfamily, with unknown expression pattern and functional significance. We report a perinatal lethal phenotype in two foetuses from the same family associated with a biallelic loss of function variant in SERPINA11, and provide functional evidence to support its candidature as a Mendelian disorder. The SERPINA11 variant-associated foetal phenotype is characterised by gross and histopathological features of extracellular matrix disruption. Western blot and immunofluorescence analyses revealed SERPINA11 expression in multiple mouse tissues, with pronounced expression in the bronchiolar epithelium. We observed a significant decrease in SERPINA11 immunofluorescence in the affected foetal lung compared with a healthy gestation-matched foetus. Protein expression data from HEK293T cell lines following site-directed mutagenesis support the loss of function nature of the variant. Transcriptome analysis from the affected foetal liver indicated the possibility of reduced SERPINA11 transcript abundance. This novel serpinopathy appears to be a consequence of the loss of inhibition of serine proteases involved in extracellular matrix remodelling, revealing SERPINA11 as a protease inhibitor critical for embryonic development.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Serpinas
Límite:
Animals
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Female
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Humans
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Male
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Pregnancy
Idioma:
En
Revista:
Clin Genet
Año:
2024
Tipo del documento:
Article
País de afiliación:
India