Familial deficiency of two subunits of the first component of complement. c1r and c1s associated with a lupus erythematosus‐like disease

Lee, Stanley L.; Wallace, Stanley L.; Barone, Richard; Blum, Livia; Chase, Peter

doi:10.1002/art.1780210813

Cited by 45 publications

(13 citation statements)

References 24 publications

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“…In addition to a low level of serum C1s, patient III-1 and her brother patient III-2 showed significantly lower levels of serum C1r. Several previous reports showed that C1s deficiency was sometimes accompanied with C1r deficiency or abnormally low C1r (5,7). In the present study, we screened for abnormalities in the C1r gene, and demonstrated that patient III-1 has no abnormalities, at least in the coding sequence of this gene.…”

Section: Discussionsupporting

confidence: 48%

“…Several cases of human complement C1 deficiency have been reported (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), in which the deficiency was caused by the absence of the subcomponents C1q (6, 9 -13), C1r (3,4,8), C1s (7, 14 -17), or both C1r and C1s (5). The molecular basis for hereditary C1q deficiency is well defined, where homozygosity for nonsense mutations in the C1q A-chain and B-chain genes (6,10,12,13) and deletion, nonsense, and missense mutations in the C1q C-chain gene (10,11) have been demonstrated.…”

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confidence: 99%

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Unique Phenotypes of C1s Deficiency and Abnormality Caused by Two Compound Heterozygosities in a Japanese Family

Abe¹,

Endo

Nakazawa

et al. 2009

The Journal of Immunology

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A deficiency in the early components of complement is associated with an increased susceptibility to pyrogenic infections and multiple autoimmune diseases. We previously reported a Japanese case of selective C1s deficiency resulting from a compound heterozygosity for a 4-bp deletion in exon X and a nonsense mutation Glu597X in exon XII of the C1s gene. In this previous case, the patient suffered from unique symptoms including virus-associated hemophagocytic syndrome and died after a long period of loss of consciousness. In the present study, we report another patient from the same family, with C1s abnormality caused by a distinct compound-heterozygous genotype and who had a novel missense mutation Gly630Glu transmitted from the mother’s side and a previously identified nonsense mutation Glu597X from the father’s side. Thus three distinct mutations of the C1s gene were clustered and resulted in two distinct genotypes for C1s deficiency and C1s abnormality within this one family. The present patient showed symptoms that were similar in part to our previous patient, which were different from those of the cases reported in other families. The biochemical properties of C1s in the patient’s serum and the recombinant form were closely related to the undetectable or very low activity of complement activation. These results suggested that the uniqueness and severity of the symptoms observed here in the two patients might be under the control of a common C1s allele and distinct counterparts, respectively.

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Section: Discussionsupporting

confidence: 48%

mentioning

confidence: 99%

Unique Phenotypes of C1s Deficiency and Abnormality Caused by Two Compound Heterozygosities in a Japanese Family

Abe¹,

Endo

Nakazawa

et al. 2009

The Journal of Immunology

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“…Virus-associated hemophagocytic syndrome was reported in another patient who died at the age of 7 years (3). Combined and partial C1s and C1r deficiency has also been reported in several patients including four siblings, two of whom developed discoid lupus and rheumatoid arthritis (18), and a 60-year-old woman with SLE (19). The genetic defect of combined C1r/C1s deficiency has not yet been elucidated but might be related to the close location of the two genes on chromosome 12 (12p13) (7).…”

Section: Discussionmentioning

confidence: 98%

Molecular Basis of a Selective C1s Deficiency Associated with Early Onset Multiple Autoimmune Diseases

Dragon-Durey

Quartier

Frémeaux‐Bacchi

et al. 2001

The Journal of Immunology

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We have investigated the molecular basis of selective and complete C1s deficiency in 2-year-old girl with complex autoimmune diseases including lupus-like syndrome, Hashimoto’s thyroiditis, and autoimmune hepatitis. This patient’s complement profile was characterized by the absence of CH50 activity, C1 functional activity <10%, and undetectable levels of C1s Ag associated with normal levels of C1r and C1q Ags. Exon-specific amplification of genomic DNA by PCR followed by direct sequence analysis revealed a homozygous nonsense mutation in the C1s gene exon XII at codon 534, caused by a nucleotide substitution from C (CGA for arginine) to T (TGA for stop codon). Both parents were heterozygous for this mutation. We used the new restriction site for endonuclease Fok-1 created by the mutation to detect this mutation in the genomic DNA of seven healthy family members. Four additional heterozygotes for the mutation were identified in two generations. Our data characterize for the first time the genetic defect of a selective and complete C1s deficiency in a Caucasian patient.

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“…To date, 6 reports of C 1 r/C 1 s deficiency (involving 1 1 people) have appeared in the literature (6). Pondman et a1 (7) reported a case of abnormal C1 in a patient with SLE, which was later reviewed as a hereditary Cls deficiency (8, 9), in which only traces of Clr activity were sometimes noted. In several cases of Clr deficiency, a low titer of Cls was identified (8)(9)(10)(11).…”

Section: Discussionmentioning

confidence: 99%

“…Pondman et a1 (7) reported a case of abnormal C1 in a patient with SLE, which was later reviewed as a hereditary Cls deficiency (8, 9), in which only traces of Clr activity were sometimes noted. In several cases of Clr deficiency, a low titer of Cls was identified (8)(9)(10)(11). Thus, from the functional and structural similarity of Clr and Cls, the term "hereditary Clr/Cls deficiency" was proposed (2).…”

Section: Discussionmentioning

confidence: 99%

Selective deficiency of c1s associated with a systemic lupus erythematosus—like syndrome. Report of a case

Suzuki

Ogura

Otsubo

et al. 1992

Arthritis & Rheumatism

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We describe a patient who developed a systemic lupus erythematosus-like syndrome characterized by bilateral malar erythema, antinuclear antibody, and anti-double-stranded DNA antibody. He was started on hemodialysis (3 timedweek) because of renal failure. He completely lacked total hemolytic complement (CH50) activity, which was subsequently determined to be due to the absence of the first component of complement (Cl). The specificity was further defined, by Ouchterlony analysis using anti-Cls antiserum, and was found to be the C1 subcomponent CIS. There was no absence of Clr. We conclude that this is a case of selective deficiency of Cls.Complement deficiency is a rare condition. To date, several cases of complement component deficiency have been reported (I). Of these individuals, some were deficient in C1 because of an absence of one of the C1 subcomponents Clq, Clr, or C l s (2). Until now, however, no patient has been found to be clearly lacking only Cls, although deficiencies of both C l r and C l s have been described (2). It is known that a defect in one of the early components of complement will often induce a systemic lupus erythematosus (SLEtlike syndrome in which there is bilateral malar erythema, positive antinuclear antibody (ANA), and positive anti-double-stranded DNA (anti-dsDNA) antibody (3). We report here a case of selective CIS deficiency in which the subject exhibited an SLE-like syndrome and renal failure. CASE REPORTThe patient, a 26-year-old man, was admitted to our hospital on June 18, 1988 because of orthopnea. Pertinent medical history included removal of his left kidney because of hydronephrosis when he was 3 months old. Data concerning the histologic features of the excised kidney were not available. At age 11, he was diagnosed as having chronic nephritis with proteinuria and hematuria. There was nothing notable in his family's medical history.At the time of admission, the patient was somewhat lethargic and orthopneic. His blood pressure was 133/73 mm Hg, and his pulse rate was 72 beatdminute and regular. He had erythema over the malar region bilaterally. The liver, spleen, and kidney were not palpable; no struma could be felt. There was slight pretibial pitting edema. The palpebral conjunctivae were anemic. No abnormality was detected on neurologic examination. A chest radiograph revealed evidence of previous tuberculosis in the right upper lung field, and an enlarged heart (cardiothoracic ratio 58%). Left ventricular ejection at rest was 14%, as determined by a cardiac pool scintigram, and a myocardial scintigram showed decreased uptake in the apex and anterior front.The total serum protein level was 5.8 g d d l , the blood urea nitrogen and serum creatinine levels were elevated (107 mg/dl and 9.4 mg/ml, respectively), and the creatinine clearance rate was decreased (5.9 mlhinute). He had proteinuria (2.5 grdday), and red blood cells were

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Familial deficiency of two subunits of the first component of complement. c1r and c1s associated with a lupus erythematosus‐like disease

Cited by 45 publications

References 24 publications

Unique Phenotypes of C1s Deficiency and Abnormality Caused by Two Compound Heterozygosities in a Japanese Family

Unique Phenotypes of C1s Deficiency and Abnormality Caused by Two Compound Heterozygosities in a Japanese Family

Molecular Basis of a Selective C1s Deficiency Associated with Early Onset Multiple Autoimmune Diseases

Selective deficiency of c1s associated with a systemic lupus erythematosus—like syndrome. Report of a case

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