C7 complement deficiency in an Israeli Arab village

Behar, Doron M.; Schlesinger, Menachem; Halle, David; Ben-Ami, Haim; Edoute, Y; Shahar, Eduardo; Kasis, Imad; Shihab, Shihab; Elstein, Deborah; Zimran, Ari; Mandel, Hanna

doi:10.1002/ajmg.10393

Cited by 13 publications

(10 citation statements)

References 21 publications

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“…Halle and coworkers found the G357R mutation among Israeli Moroccan Jewish individuals 18 . The mutation was found also in two siblings with C7 deficiency from a highly inbred Arab population living in the lower Galilee region of Israel, a place where Sephardic Jews have lived for many generations 19 and very recently in two heterozygous C7 deficient siblings in our population 14 . Interestingly, patient 1 was from Gypsy ethnical background.…”

Section: Discussionsupporting

confidence: 62%

“…This deletion generates a downstream stop codon, UGA, which leads to the premature truncation of the encoded C7 protein (K416 X 419). Additionally, we found in patient 1 a previously described missense mutation at cDNA nucleotide 1135 located in exon 9 16–19 . This position is the first nucleotide of the codon GGG for Gly 357 of normal C7 (Fig.…”

Section: Detection Of C7 Gene Mutationsmentioning

confidence: 53%

“…and the position of mutations described to date (numbered from 1 to 15), and the two novel mutations found in our study (16,17). Mutations described previously: 1, G>A transition at the 3′ acceptor site of intron 1; 17 2, R198Q; 21 3, deletion of around 6·8 kbp including exons 7 and 8; 17 ; 22 4, a G>A transversion at the 5′ splice donor site of intron 7; 21,23 5, G357R; 14,17–19 6, R499S; 24 7, 1929delC; 21 8, E631X; 13 9, E660Q; 21 10, R665H; 21 11, 2137delTG or 2138delGT/2139delTG; 12 12, C728X; 12 13, 2350delG; 21 14, T>C transversion at the splice donor site of intron 16; 21,23 15, W183X 14 . Circled mutations 5, 16 and 17 indicate mutations found in the patients in this study.…”

Section: Discussionmentioning

confidence: 96%

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Complement component C7 deficiency in two Spanish families

et al. 2004

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Summary Different genetic mutations have been described in complement component C7 deficiency, a molecular defect clinically associated with an increased susceptibility to neisserial recurrent infections. In this work we report the genetic basis of C7 deficiency in two different Spanish families (family 1 and family 2). In family 1, of Gypsy ethnical background, exon‐specific polymerase chain reaction and sequencing revealed a not previously described single base deletion of nucleotide 1309 (exon 10) in the patient, as well as in her father, leading to a stop codon that causes the premature truncation of the C7 protein (K416 X 419). Additionally, the patient and her mother displayed a missense mutation at position 1135 (exon 9) located in the first nucleotide of the codon GGG (CGG), resulting in a change of amino acid (G357R). This mutation was firstly described in individuals of Moroccan Sephardic Jewish ancestry and has been also reported among Spaniards. In family 2, another novel mutation was found in homozygosity in two siblings; a two base‐pair deletion of nucleotides 1922 and 1923 in exon 14 leading to the generation of a downstream stop codon causing the truncation of the C7 protein product (S620 X 630). Our results provide more evidence for the heterogeneous molecular basis of C7 deficiency as well as for the subsequent susceptibility to meningococcal disease, since different families carry different molecular defects. On the other hand, certain C7 defects appear to be prevalent in individuals from certain populations or living in defined geographical areas.

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Section: Discussionsupporting

confidence: 62%

Section: Detection Of C7 Gene Mutationsmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Complement component C7 deficiency in two Spanish families

et al. 2004

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“…The C7 gene spans about 80 kb of DNA and is encoded by 18 exons (10). To date, more than 15 different molecular defects leading to total or subtotal C7 deficiency have been reported (11, 12). Here we report two novel mutations of the gene in a Korean family with C7 deficiency.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, there appears to be an ethnic predilection for specific terminal complement deficiencies: C6 and C8α-γ deficiencies are common in blacks, whereas C7 and C8β deficiencies are predominantly observed in Caucasians. The cases of C7 deficiency have been reported more frequently in Spanish, Israeli, and Irish than in Asians in Japan and Korea (6, 7, 11, 12). …”

Section: Discussionmentioning

confidence: 99%

Two Novel Mutations in the C7 gene in a Korean Patient with Complement C7 Deficiency

Kim

et al. 2005

J Korean Med Sci

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Complement C7 deficiency is an autosomal recessive disorder well known to be associated with increased susceptibility to meningococcal infection and has mostly been reported in Caucasians. In the Korean population, no case of C7 deficiency has been reported to date. Recently we experienced an 11-yr-old girl with meningococcal meningitis who was diagnosed as having C7 deficiency based upon the undetectable serum C7 protein on radial immunodiffusion and the undetectable serum total and C7 hemolytic activities. To identify the genetic basis of the C7 deficiency of the patient, we performed a mutation analysis for the C7 gene and found two novel mutations; a point mutation at the 3' splice acceptor site of intron 4 (c.281-1G>T) and a large deletion mutation encompassing almost the whole C7 gene from exon 1 to exon 17 (c.1-?_2350+?del). A haplotype analysis showed that the large deletion mutation was inherited from the patient's father. To the best of our knowledge, this is the first confirmed case of C7 deficiency in Korea.

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Hereditary complement C7 deficiency in nine families: Subtotal C7 deficiency revisited

et al. 2007

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Deficiencies in terminal complement components, including the component C7, are uncommon and associated with an increased risk of recurrent systemic neisserial infection. A total of 22 molecular defects have been reported in the C7 gene with both complete (C7Q0) and subtotal (C7SD) C7 deficiencies. In this study we report the molecular basis of nine new cases of C7 deficiencies that were characterized by exonspecific sequence analysis. Seven different C7 gene mutations were identified corresponding to small deletions (n=2), splice site changes (n=1) and single base pair substitutions leading to nonsense (n=1) or missense (n=3) mutations. Altogether, three changes of the C7 gene (G357R, R499S and 5 0 splice donor site of intron 16) account for half of the molecular defects which emphasize that a restricted number of molecular abnormalities are involved in this deficiency. We identified two patients with combined C7Q0/C7SD(R499S) and established the C7SD(R499S) frequency at about 1% in normal Caucasian population. We demonstrated that C7(R499S) mutant protein is retained in the endoplasmic reticulum whereas the wild-type C7 is located in the Golgi apparatus. Our results provide evidence that R499S represents a loss-of-function polymorphism of C7 due to a defective folding of the protein.

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C7 complement deficiency in an Israeli Arab village

Cited by 13 publications

References 21 publications

Complement component C7 deficiency in two Spanish families

Complement component C7 deficiency in two Spanish families

Two Novel Mutations in the C7 gene in a Korean Patient with Complement C7 Deficiency

Hereditary complement C7 deficiency in nine families: Subtotal C7 deficiency revisited

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