Leddy et al. (1974) and Heusinkveld et al. (1974) described C6 deficiency in an 18-year-old woman in good general health. Her serum lacked hemolytic complement activity. The action of an abnormal inhibitor was excluded. Both parents and 5 ... Leddy et al. (1974) and Heusinkveld et al. (1974) described C6 deficiency in an 18-year-old woman in good general health. Her serum lacked hemolytic complement activity. The action of an abnormal inhibitor was excluded. Both parents and 5 of 6 sibs had about half the normal levels of functional C6. Unlike C6 deficiency in rabbits, no abnormality of clotting was demonstrated. Ellison et al. (1983) commented that about half the reported congenital deficiencies of terminal complement proteins have occurred in black patients. Their own studies of 20 cases of sporadic meningococcal disease uncovered 2 with C6 deficiency.
Hobart et al. (1998), Zhu et al. (1998), and Nishizaka et al. (1996) reported mutations in the C6 gene resulting in total C6 deficiency (see 217050.0003, 217050.0004, and 217050.0005).
- Subtotal C6 Deficiency
Individuals ... Hobart et al. (1998), Zhu et al. (1998), and Nishizaka et al. (1996) reported mutations in the C6 gene resulting in total C6 deficiency (see 217050.0003, 217050.0004, and 217050.0005). - Subtotal C6 Deficiency Individuals with subtotal C6 deficiency possess a C6 molecule that is 14% shorter than normal C6 and present in low but detectable concentrations in serum (1 to 2% of the normal mean). Wurzner et al. (1995) identified a mutation in the C6 gene in 3 individuals with subtotal C6 deficiency from 2 families. All 3 had an abnormal 5-prime splice donor site of intron 15 predicted to prevent splicing (217050.0002). An in-frame stop codon was found 17 codons downstream from the intron boundary, which would lead to a truncated polypeptide 140 amino acids (13.5%) smaller than the normal C6. All 3 subjects were probably heterozygous for both subtotal C6 and complete C6 deficiency. In individuals with combined subtotal deficiency of C6 and C7 (610102), Fernie et al. (1996) identified mutations in both C6 (IVS15+2T-C; 217050.0002) and C7 (arg499 to ser; 217070.0003) on a characteristic haplotype. Fernie et al. (1996) proposed an integrated model explaining the molecular bases of combined subtotal deficiency of C6 and C7 and described the effects of these molecular defects in isolation.
By screening for complement deficiencies in 145,640 blood donors from Osaka and combining their results with reports of 92,686 donors from throughout Japan, Fukumori and Horiuchi (1998) identified 5 individuals with C5 deficiency (609536), 6 individuals with C6 ... By screening for complement deficiencies in 145,640 blood donors from Osaka and combining their results with reports of 92,686 donors from throughout Japan, Fukumori and Horiuchi (1998) identified 5 individuals with C5 deficiency (609536), 6 individuals with C6 deficiency, 17 individuals with C7 deficiency (610102), 5 individuals with C8 alpha/gamma deficiency (613790), and 439 individuals with C9 deficiency (613825). A heterozygous 1-bp deletion in exon 2 of the C6 gene (217050.0006) had been identified by Nishizaka et al. (1996) in 1 of the Japanese individuals with C6 deficiency. The putative mutation in the other C6 allele of this individual had not been identified.