Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012872 (DNA marker)
 929 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ninth component of human complement (C9) is the last of the terminal complement components creating the membrane attack complex. C9 is a single-chain serum protein that is encoded by a gene located on chromosome 5p. Deficiency of terminal complement components is generally associated with recurrent neisseria infections. We studied a previously described Swiss family with inherited C9 deficiency. To identify the genetic basis of C9 deficiency, we developed an approach using exon-specific PCR and direct DNA sequencing. As a cause of C9 deficiency, we found two different point mutations, both generating TGA stop codons in the coding sequence. One mutation, a C to A exchange, was detected in exon 2 at cDNA position 166, the other, a C to T exchange, was located in exon 4 (cDNA position 464). In family studies of three first-degree relatives with heterozygous C9 deficiency, we demonstrated that the two mutations are segregating independently. Therefore, these mutations are sufficient to explain the complete deficiency of both the probands studied. DNA sequencing of the exon-intron junctions revealed a number of revisions regarding the boundaries between exons 4, 5, and 6 as well as between exons 10 and 11. No additional introns were detected in exons 6 and 10. Furthermore, DNA marker studies were conducted using known polymorphisms of the C6, C7, and C9 genes, confirming the linkage of the observed C9 mutations with defined haplotypes.
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PMID:The human complement C9 gene: identification of two mutations causing deficiency and revision of the gene structure. 914 25

Deficiency of the sixth component of human complement (C6) has been reported in a number of families from the western Cape, South Africa. Meningococcal disease is endemic in the Cape and almost all pedigrees of total C6 deficiency (C6Q0) have been ascertained because of recurrent disease. We have sequenced the expressed exons of the C6 gene from selected cases and have found three molecular defects leading to total deficiency: 879delG, which is the common defect in the Cape and hitherto unreported, and 1195delC and 1936delG, which have been previously reported in African-Americans. We also show that the 879delG and 1195delC defects are associated with characteristic C6/C7 region DNA marker haplotypes, although small variations were observed. The 1936delG defect was observed only once in the Cape, but its associated haplotype could be deduced. The data from the haplotypes indicate that these three molecular defects account for the defects in all the 38 unrelated C6Q0 individuals we have studied from the Cape. We have also observed the 879delG defect in two Dutch C6-deficient kindreds, but the 879delG defect in the Cape probably did not come from The Netherlands.
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PMID:The molecular basis of C6 deficiency in the western Cape, South Africa. 985 98