CompoundSFTPB 1549C?GAA (121ins2) and 457delC heterozygosity in severe congenital lung disease and surfactant protein B (SP-B) deficiency

GAA, or 121ins2) of the SP-B-encoding gene (SFTPB) results in rapidly fatal respiratory failure, with complete absence of the mRNA and protein observed in lung fluid or biopsy specimens. Hereditary SP-B deficiency is also associated with aberrant processing of proSP-C and deficiency of the active SP-C peptide. In the present study, we characterized the SFTPB gene in an infant with severe unexplained respiratory distress and identified a paternally derived 1549C-->GAA lesion, as well as a hitherto unreported mutation (457delC) inherited from the mother. Analysis of bronchoalveolar lavage fluid demonstrated the complete absence of SP-B, However, unlike previous infants with hereditary SP-B deficiency, proSP-C was processed to the active SP-C peptide, suggesting that the defect in SP-B, rather than SP-C, caused the respiratory distress in this infant. The present findings demonstrate the importance of SFTPB in pulmonary function and support the need for further genotype-phenotype correlations in patients with SP-B deficiency. Hum Mutat 14:502-509, 1999, (C) 1999 Wiley Liss, Inc -->
ISSN: 1098-1004
1059-7794
DOI: 10.1002/(sici)1098-1004(199912)14:6<502::aid-humu9>3.0.co;2-c
Přístupová URL adresa: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::26700933077c3119c6b925b07313123e
https://doi.org/10.1002/(sici)1098-1004(199912)14:6<502::aid-humu9>3.0.co;2-c
Rights: RESTRICTED
Přírůstkové číslo: edsair.doi.dedup.....26700933077c3119c6b925b07313123e
Autor: Pierre Aymard, Claude Houdayer, M Tredano, Ruurd M. van Elburg, Jeffrey A. Whitsett, Matthias Griese, Michel Bahuau, Ageeth G. Kaspers, William M. Hull, Jacques Elion, Luc J I Zimmermann
Přispěvatelé: Other departments
Rok vydání: 1999
Předmět:
Zdroj: Human mutation, 14(6), 502-509. Wiley-Liss Inc.
ISSN: 1098-1004
1059-7794
DOI: 10.1002/(sici)1098-1004(199912)14:6<502::aid-humu9>3.0.co;2-c
Popis: Several human respiratory disorders have been linked to an abnormality of pulmonary surfactant synthesis or turnover. Among those conditions, hereditary deficiency in the hydrophobic surfactant protein B (SP-B) has been recognized as a rare cause of respiratory failure in term newborn infants. Homozygosity for a common mutation (1549C-->GAA, or 121ins2) of the SP-B-encoding gene (SFTPB) results in rapidly fatal respiratory failure, with complete absence of the mRNA and protein observed in lung fluid or biopsy specimens. Hereditary SP-B deficiency is also associated with aberrant processing of proSP-C and deficiency of the active SP-C peptide. In the present study, we characterized the SFTPB gene in an infant with severe unexplained respiratory distress and identified a paternally derived 1549C-->GAA lesion, as well as a hitherto unreported mutation (457delC) inherited from the mother. Analysis of bronchoalveolar lavage fluid demonstrated the complete absence of SP-B, However, unlike previous infants with hereditary SP-B deficiency, proSP-C was processed to the active SP-C peptide, suggesting that the defect in SP-B, rather than SP-C, caused the respiratory distress in this infant. The present findings demonstrate the importance of SFTPB in pulmonary function and support the need for further genotype-phenotype correlations in patients with SP-B deficiency. Hum Mutat 14:502-509, 1999, (C) 1999 Wiley Liss, Inc
Databáze: OpenAIRE
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