title: The molecular basis of hereditary complement factor I deficiency.
abstract: The molecular basis of hereditary complement factor I deficiency is described in two pedigrees. In one pedigree, there were two factor I-deficient siblings, one of whom was asymptomatic and the other suffered from recurrent pyogenic infections. Their factor I mRNA was analyzed by reverse transcription of fibroblast RNA followed by amplification using the polymerase chain reaction. Both siblings were homozygous for the same transversion (adenine to thymine) at nucleotide 1282 in the cDNA. This mutation causes histidine-400 to be replaced by leucine. The altered histidine is a semi-conserved residue within the serine proteinase family, although no function has been ascribed to it. The proband of the second pedigree studied was found to be a compound heterozygote. One allele had the same mutation as the first family, the second allele had a donor splice site mutation that resulted in the deletion of the mRNA encoded in the fifth exon (a low-density lipoprotein receptor domain) from its transcript.
authors.affiliation: Department of Medicine, RPMS, Hammersmith Hospital, London, United Kingdom.
authors.forename: T J
authors.initials: TJ
authors.lastname: Vyse
authors.forename: B J
authors.initials: BJ
authors.lastname: Morley
authors.forename: I
authors.initials: I
authors.lastname: Bartok
authors.forename: E L
authors.initials: EL
authors.lastname: Theodoridis
authors.forename: K A
authors.initials: KA
authors.lastname: Davies
authors.forename: A D
authors.initials: AD
authors.lastname: Webster
authors.forename: M J
authors.initials: MJ
authors.lastname: Walport
mesh_terms: D000483:Alleles; D001483:Base Sequence; D001778:Blood Coagulation Disorders / Q000235:genetics*; D002648:Child; D017244:Complement Factor I / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D013329:Structure-Activity Relationship
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D017244:Complement Factor I