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Genetic analysis of complement C1s deficiency associated with systemic lupus erythematosus highlights alternative splicing of normal C1s gene

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Genetic analysis of complement C1s deficiency associated with systemic lupus erythematosus highlights alternative splicing of normal C1s gene. / Amano, Mariane T; Ferriani, Virgínia P L; Florido, Marlene P C; Reis, Edimara S; Delcolli, Maria I M V; Azzolini, Ana E C S; Assis-Pandochi, Ana I; Sjöholm, Anders G; Farah, Chuck S; Jensenius, Jens Christian; Isaac, Lourdes.

In: Molecular Immunology, Vol. 45, No. 6, 2008, p. 1693-702.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Amano, MT, Ferriani, VPL, Florido, MPC, Reis, ES, Delcolli, MIMV, Azzolini, AECS, Assis-Pandochi, AI, Sjöholm, AG, Farah, CS, Jensenius, JC & Isaac, L 2008, 'Genetic analysis of complement C1s deficiency associated with systemic lupus erythematosus highlights alternative splicing of normal C1s gene', Molecular Immunology, vol. 45, no. 6, pp. 1693-702. https://doi.org/10.1016/j.molimm.2007.09.034

APA

Amano, M. T., Ferriani, V. P. L., Florido, M. P. C., Reis, E. S., Delcolli, M. I. M. V., Azzolini, A. E. C. S., Assis-Pandochi, A. I., Sjöholm, A. G., Farah, C. S., Jensenius, J. C., & Isaac, L. (2008). Genetic analysis of complement C1s deficiency associated with systemic lupus erythematosus highlights alternative splicing of normal C1s gene. Molecular Immunology, 45(6), 1693-702. https://doi.org/10.1016/j.molimm.2007.09.034

CBE

Amano MT, Ferriani VPL, Florido MPC, Reis ES, Delcolli MIMV, Azzolini AECS, Assis-Pandochi AI, Sjöholm AG, Farah CS, Jensenius JC, Isaac L. 2008. Genetic analysis of complement C1s deficiency associated with systemic lupus erythematosus highlights alternative splicing of normal C1s gene. Molecular Immunology. 45(6):1693-702. https://doi.org/10.1016/j.molimm.2007.09.034

MLA

Vancouver

Amano MT, Ferriani VPL, Florido MPC, Reis ES, Delcolli MIMV, Azzolini AECS et al. Genetic analysis of complement C1s deficiency associated with systemic lupus erythematosus highlights alternative splicing of normal C1s gene. Molecular Immunology. 2008;45(6):1693-702. https://doi.org/10.1016/j.molimm.2007.09.034

Author

Amano, Mariane T ; Ferriani, Virgínia P L ; Florido, Marlene P C ; Reis, Edimara S ; Delcolli, Maria I M V ; Azzolini, Ana E C S ; Assis-Pandochi, Ana I ; Sjöholm, Anders G ; Farah, Chuck S ; Jensenius, Jens Christian ; Isaac, Lourdes. / Genetic analysis of complement C1s deficiency associated with systemic lupus erythematosus highlights alternative splicing of normal C1s gene. In: Molecular Immunology. 2008 ; Vol. 45, No. 6. pp. 1693-702.

Bibtex

@article{a3a09c3c48744a1c8c293ecd22fc8ffc,
title = "Genetic analysis of complement C1s deficiency associated with systemic lupus erythematosus highlights alternative splicing of normal C1s gene",
abstract = "Deficiencies of complement proteins of the classical pathway are strongly associated with the development of autoimmune diseases. Deficiency of C1r has been observed to occur concomitantly with deficiency in C1s and 9 out of 15 reported cases presented systemic lupus erythematosus (SLE). Here, we describe a family in which all four children are deficient in C1s but only two of them developed SLE. Hemolytic activity mediated by the alternative and the lectin pathways were normal, but classical pathway activation was absent in all children's sera. C1s was undetectable, while in the parents' sera it was lower than in the normal controls. The levels of C1r observed in the siblings and parents sera were lower than in the control, while the concentrations of other complement proteins (C3, C4, MBL and MASP-2) were normal in all family members. Impairment of C1s synthesis was observed in the patients' fibroblasts when analyzed by confocal microscopy. We show that all four siblings are homozygous for a mutation at position 938 in exon 6 of the C1s cDNA that creates a premature stop codon. Our investigations led us to reveal the presence of previously uncharacterized splice variants of C1s mRNA transcripts in normal human cells. These variants are derived from the skipping of exon 3 and from the use of an alternative 3' splice site within intron 1 which increases the size of exon 2 by 87 nucleotides.",
keywords = "Adult, Alternative Splicing, Base Sequence, Cells, Cultured, Child, Complement C1s, Exons, Female, Fibroblasts, Humans, Introns, Lupus Erythematosus, Systemic, Male, Molecular Sequence Data, Pedigree, RNA, Messenger",
author = "Amano, {Mariane T} and Ferriani, {Virg{\'i}nia P L} and Florido, {Marlene P C} and Reis, {Edimara S} and Delcolli, {Maria I M V} and Azzolini, {Ana E C S} and Assis-Pandochi, {Ana I} and Sj{\"o}holm, {Anders G} and Farah, {Chuck S} and Jensenius, {Jens Christian} and Lourdes Isaac",
year = "2008",
doi = "10.1016/j.molimm.2007.09.034",
language = "English",
volume = "45",
pages = "1693--702",
journal = "Molecular Immunology",
issn = "0161-5890",
publisher = "Pergamon Press",
number = "6",

}

RIS

TY - JOUR

T1 - Genetic analysis of complement C1s deficiency associated with systemic lupus erythematosus highlights alternative splicing of normal C1s gene

AU - Amano, Mariane T

AU - Ferriani, Virgínia P L

AU - Florido, Marlene P C

AU - Reis, Edimara S

AU - Delcolli, Maria I M V

AU - Azzolini, Ana E C S

AU - Assis-Pandochi, Ana I

AU - Sjöholm, Anders G

AU - Farah, Chuck S

AU - Jensenius, Jens Christian

AU - Isaac, Lourdes

PY - 2008

Y1 - 2008

N2 - Deficiencies of complement proteins of the classical pathway are strongly associated with the development of autoimmune diseases. Deficiency of C1r has been observed to occur concomitantly with deficiency in C1s and 9 out of 15 reported cases presented systemic lupus erythematosus (SLE). Here, we describe a family in which all four children are deficient in C1s but only two of them developed SLE. Hemolytic activity mediated by the alternative and the lectin pathways were normal, but classical pathway activation was absent in all children's sera. C1s was undetectable, while in the parents' sera it was lower than in the normal controls. The levels of C1r observed in the siblings and parents sera were lower than in the control, while the concentrations of other complement proteins (C3, C4, MBL and MASP-2) were normal in all family members. Impairment of C1s synthesis was observed in the patients' fibroblasts when analyzed by confocal microscopy. We show that all four siblings are homozygous for a mutation at position 938 in exon 6 of the C1s cDNA that creates a premature stop codon. Our investigations led us to reveal the presence of previously uncharacterized splice variants of C1s mRNA transcripts in normal human cells. These variants are derived from the skipping of exon 3 and from the use of an alternative 3' splice site within intron 1 which increases the size of exon 2 by 87 nucleotides.

AB - Deficiencies of complement proteins of the classical pathway are strongly associated with the development of autoimmune diseases. Deficiency of C1r has been observed to occur concomitantly with deficiency in C1s and 9 out of 15 reported cases presented systemic lupus erythematosus (SLE). Here, we describe a family in which all four children are deficient in C1s but only two of them developed SLE. Hemolytic activity mediated by the alternative and the lectin pathways were normal, but classical pathway activation was absent in all children's sera. C1s was undetectable, while in the parents' sera it was lower than in the normal controls. The levels of C1r observed in the siblings and parents sera were lower than in the control, while the concentrations of other complement proteins (C3, C4, MBL and MASP-2) were normal in all family members. Impairment of C1s synthesis was observed in the patients' fibroblasts when analyzed by confocal microscopy. We show that all four siblings are homozygous for a mutation at position 938 in exon 6 of the C1s cDNA that creates a premature stop codon. Our investigations led us to reveal the presence of previously uncharacterized splice variants of C1s mRNA transcripts in normal human cells. These variants are derived from the skipping of exon 3 and from the use of an alternative 3' splice site within intron 1 which increases the size of exon 2 by 87 nucleotides.

KW - Adult

KW - Alternative Splicing

KW - Base Sequence

KW - Cells, Cultured

KW - Child

KW - Complement C1s

KW - Exons

KW - Female

KW - Fibroblasts

KW - Humans

KW - Introns

KW - Lupus Erythematosus, Systemic

KW - Male

KW - Molecular Sequence Data

KW - Pedigree

KW - RNA, Messenger

U2 - 10.1016/j.molimm.2007.09.034

DO - 10.1016/j.molimm.2007.09.034

M3 - Journal article

C2 - 18062908

VL - 45

SP - 1693

EP - 1702

JO - Molecular Immunology

JF - Molecular Immunology

SN - 0161-5890

IS - 6

ER -