Familial C1q deficiency associated with renal and cutaneous disease

Area of Science:

• Immunology
• Genetics
• Nephrology

Background:

• Familial C1q deficiency is a rare genetic disorder affecting the complement system.
• Complement system defects are linked to autoimmune diseases and increased infection susceptibility.
• Rothmund-Thomson syndrome (poikiloderma congenital) is a rare genodermatosis with diverse clinical manifestations.

Purpose of the Study:

• To characterize a novel familial C1q deficiency in three siblings.
• To investigate the association between C1q deficiency, Rothmund-Thomson syndrome, and mesangial proliferative glomerulonephritis.
• To define the immunological and biochemical characteristics of the complement defect.

Main Methods:

• Clinical and pathological evaluation of affected siblings.
• Hemolytic complement assays (CH50) to assess complement activity.
• Quantification of complement components (C1q, C2, C3, C4, C5) using functional and immunochemical methods.
• Assessment of complement component function through complement reconstitution assays.

Main Results:

• Established a familial C1q deficiency in three siblings (two brothers, one sister).
• Patients exhibited clinical and pathological features of Rothmund-Thomson syndrome and mesangial proliferative glomerulonephritis with diffuse IgM deposits.
• Demonstrated a total lack of CH50 hemolytic activity and undetectable C1q levels.
• Confirmed normal levels of C2, C3, C4, and C5, with no correction of the defect by adding purified C2-C9.
• Restored CH50 hemolytic activity upon addition of purified human C1q, confirming C1q as the deficient component.

Conclusions:

• The study identified a complete C1q deficiency as the cause of the observed clinical phenotype in three siblings.
• This case underscores the critical role of the C1q molecule in complement-mediated immunity and kidney homeostasis.
• The co-occurrence of C1q deficiency with Rothmund-Thomson syndrome and glomerulonephritis suggests potential genotype-phenotype correlations or shared pathogenic mechanisms.