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

Ki, Chang‐Seok; Kim, Jong-Won; Kim, Hee‐Jin; Choi, Sung-Min; Ha, Gyoung-Yim; Kang, Hee Jung; Kim, Won-Duck

doi:10.3346/jkms.2005.20.2.220

Cited by 10 publications

(6 citation statements)

References 22 publications

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“…To date, 19 different molecular defects leading to total or subtotal C7 deficiency defects have been reported 17,21 , 22 . Here we report two novel mutations in the C7 gene in two unrelated individuals with C7 deficiency leading to undetectable CH50 activity.…”

Section: Resultsmentioning

confidence: 81%

Molecular defects of the C7 gene in two patients with complement C7 deficiency

et al. 2006

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Summary Different genetic mutations have been described in complement components resulting in total or subtotal deficiency states. In this work we report the genetic basis of C7 deficiency in a previously reported Spanish patient exhibiting a combined total deficiency of C7 and C4B associated with systemic lupus erythematosus. Exon‐specific polymerase chain reaction and sequencing revealed a not previously described single base mutation in exon 10 (T1458A) leading to a stop codon that causes the premature truncation of the C7 protein (C464X). Additionally, a C to A transversion at position 1561 (exon 11) was found in the patient resulting in an amino acid change (R499S). This latter mutation has been previously reported in individuals with subtotal C7 deficiency or with combined subtotal C6/C7 deficiency from widely spaced geographical areas. Another novel mutation was found in a second patient with meningococcal meningitis of Bolivian and Czech origin; a 11‐base pair deletion of nucleotides 631–641 in exon 6 leading to the generation of a downstream stop codon causing the premature truncation of the C7 protein product (T189 × 193). This patient was found to be a heterozygous compound for another mutation in C7; a two‐base pair deletion of nucleotides 1922 and 1923, 1923 and 1924 or 1924 and 1925 in exon 14 (1922delAG/1923delGA/1924delAG), leading again to the generation of a downstream stop codon that provokes the truncation of the C7 protein (S620×630). This latter mutation has been recently reported by our group in another Spanish family. Our results provide more evidences for the heterogeneous molecular basis of C7 deficiency.

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Section: Resultsmentioning

confidence: 81%

Molecular defects of the C7 gene in two patients with complement C7 deficiency

et al. 2006

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“…Molecular characterization of 27 cases of total or subtotal C7 deficiencies have been previously reported and 22 different molecular defects in C7 gene are currently known [9][10][11][12][13]17]. Molecular mechanisms of nine new cases of C7 deficiency are reported in this study.…”

Section: Discussionmentioning

confidence: 98%

“…To date, 22 molecular defects associated to complete (C7Q0) or subtotal (C7SD) C7 deficiencies have been reported. Five cases of C7SD resulting from R499S substitution and one case resulting from R198E, both defined by very low levels of C7, have been described [9][10][11][12][13]. The R499S mutation was reported alone or combined with a subtotal C6 deficiency (C6SD), a mutation located at the 5 0 splice donor site of intron 15 of the C6 gene, which also leads to very low levels of C6 [14].…”

Section: Introductionmentioning

confidence: 99%

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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“…Homozygous but not heterozygous mutation c.281-1G>T has been previously reported to cause C7 deficiency. [ 19 ] The alanine-485 is well preserved in vertebrate animals, suggesting that the novel variant c.1454C>T (p.A485V) is contributing to C7 deficiency in a compound-heterozygous manner in our case. CH50 recovery by adding purified C7 to the patient's serum supports this hypothesis.…”

Section: Discussionmentioning

confidence: 72%

Disseminated gonococcal infection in a Japanese man with complement 7 deficiency with compound heterozygous variants

Kageyama¹,

Hagiya

Ueda

et al. 2021

Medicine

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Rationale: Complement deficiency are known to be predisposed to disseminated gonococcal infection (DGI). We herein present a case of DGI involving a Japanese man who latently had a complement 7 deficiency with compound heterozygous variants. Patient concerns: A previously healthy 51-year-old Japanese man complained of sudden-onset high fever. Physical examination revealed various skin lesions including red papules on his trunk and extremities, an impetigo-like pustule on left forearm, and tendinitis of his right forefinger. Diagnosis: Blood culture testing detected gram-negative cocci, which was confirmed to be Neisseria gonorrhoeae based on mass spectrometry and a pathogen-specific PCR test. Interventions: Screening tests for underlying immunocompromised factors uncovered that complement activities (CH50) was undetectable. With a suspicion of a congenital complement deficiency, genetic analysis revealed rare single nucleotide variants in complement 7 (C7), including c.281-1G>T and a novel variant c.1454C>T (p.A485V). CH50 was normally recovered by adding purified human C7 to the patient's serum, supporting that the patient has C7 deficiency with compound heterozygous variants. Outcomes: Under a diagnosis of DGI, the patient underwent an antibiotic treatment with cefotaxime for a week and was discharged without any sequela. Lessons: DGI is a rare sexually-transmitted infection that potentially induces systemic complications. Complement immunity usually defeats N. gonorrhoeae and prevents the organism from causing DGI. This case highlighted the importance of suspecting a complement deficiency when a person develops DGI.

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

Cited by 10 publications

References 22 publications

Molecular defects of the C7 gene in two patients with complement C7 deficiency

Molecular defects of the C7 gene in two patients with complement C7 deficiency

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

Disseminated gonococcal infection in a Japanese man with complement 7 deficiency with compound heterozygous variants

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