Complex medical history of a patient with a compound heterozygous mutation in C1QC

Abstract

Introduction: C1q is an essential part of the classical pathway of complement activation. Genetic deficiencies, caused by homozygous mutations in one of the C1q genes, are rare and are strongly associated with development of systemic lupus erythematosus (SLE). Here we describe a C1q-deficient patient with a compound heterozygous mutation.

Material and methods: Serum was analysed with enzyme-linked immunosorbent assay (ELISA) and Western blot for the presence of C1q, and DNA and RNA sequencing was performed to identify the mutations and confirm that these were located on different chromosomes.

Results: The medical history of the patient includes SLE diagnosis at age 11 years with cerebral involvement at age 13, various infections, osteonecrosis and hemophagocytic syndrome. Using ELISA and Western blot, we confirmed the absence of C1q in the serum of the patient. Using DNA sequencing, two mutations in the C1QC gene were identified: c.100G > A p.(Gly34Arg) and c.205C > T p.(Arg69X). With RNA sequencing we confirmed that the mutations are located on different chromosomes.

Discussion: The patient described in this case report has a compound heterozygous mutation in C1QC resulting in C1q deficiency.

Keywords: C1q deficiency; FFP; SLE; compound heterozygous; mutation.

Figure 1

C1q protein analysis shows no C1q in the patient’s serum. Western blot analysis of serum from the patient and a control (normal human serum). The serum samples were prepared under (a) reducing condition, (b) denaturing and non-reduced condition or (c) non-reducing and non-denaturing conditions. Measurement of C1q with enzyme-linked immunosorbent assay in the serum of healthy female age-matched controls (n = 21) and (d) the patient.

Figure 2

Compound heterozygous mutation located in the C1QC gene. RNA sequence analysis revealed heterozygous mutations of C1QC highlighted by the red box: c.100G > A p.(Gly34Arg) and c.205C > T p.(Arg69X).