Concomitant deficiences of complement factor H regulatory protein and C9 component.

Author(s)

Dayseanne Araujo Falcão

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2007-06-28

Examining board members

Lourdes Isaac; Jose Alexandre Marzagao Barbuto; Marcelo de Franco; Cristina Miuki Abe Jacob; Lucile Maria Floeter Winter

• Advisor: Lourdes Isaac

Abstract

Our proband, Brazilian from a family of Japanese descent and history of consanguinity, carries C9 (C9D) and FH deficiencies. He was referred with severe recurrent pneumonia. FH (16,8 µg/mL), C3 and FB were present in the patient at low levels. Western blot assays confirmed the complete absence of 150 kDa (FH). His mother also had FH (140,5 µg/mL), C3 and FB low levels, while his father and sister presented only FH low levels. C9 was present in low levels (5,6 µg/mL) and only a very faint ~70 kDa band (expected size) was detected. Sequencing of proband?s FH cDNA revealed a homozygous G453A substitution, encoding a His127Arg. This substitution is also homozygous in the mother and may alter FH protein tertiary structure and/or its secretion profile, as we detected FH production in patient?s fibroblast. Sequencing of proband?s C9 genomic DNA fragments revealed the absence of Arg95 mutation, main cause of C9D in other C9D Japanese patients. The proband carries a missense mutation that may impair the FH secretion, but we couldn?t identify mutations explaining its C9D. (AU)