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SERPINA11 related novel serpinopathy - A perinatal lethal disorder.
Aggarwal, Shagun; Vineeth, Venugopal Satidevi; Padwal, Shrutika S; Bhat, Sameer Ahmed; Singh, Arpita; Kulkarni, Aditya; Patil, Mallikarjun; Tallapaka, Karthik; Pasumarthi, Divya; Venkatapuram, Vijayasree; Thotakura, Pragna Lakshmi; Dalal, Ashwin; Bhandari, Rashna.
Afiliación
  • Aggarwal S; Department of Medical Genetics, Nizam's Institute of Medical Sciences, Hyderabad, India.
  • Vineeth VS; Laboratory of Human and Medical Genetics, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
  • Padwal SS; Laboratory of Human and Medical Genetics, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
  • Bhat SA; Laboratory of Human and Medical Genetics, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
  • Singh A; Laboratory of Cell Signalling, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
  • Kulkarni A; Manipal Academy of Higher Education, Manipal, India.
  • Patil M; Laboratory of Cell Signalling, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
  • Tallapaka K; Laboratory of Cell Signalling, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
  • Pasumarthi D; Regional Centre for Biotechnology, Faridabad, India.
  • Venkatapuram V; Department of Histopathology, Apollo Hospitals, Hyderabad, India.
  • Thotakura PL; Department of Medical Genetics, Nizam's Institute of Medical Sciences, Hyderabad, India.
  • Dalal A; CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
  • Bhandari R; Laboratory of Human and Medical Genetics, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
Clin Genet ; 106(3): 367-373, 2024 Sep.
Article en En | 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Serpinas / Genes Letales Límite: Animals / Female / Humans / Male / Pregnancy Idioma: En Revista: Clin Genet Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Dinamarca
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Serpinas / Genes Letales Límite: Animals / Female / Humans / Male / Pregnancy Idioma: En Revista: Clin Genet Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Dinamarca