CFH
The Clinical
Diagnostics Service of
the Molecular Otolaryngology Research Laboratory is a Joint
Commission-approved CLIA-accredited diagnostic laboratory that
offers mutation screening of several genes.
Complement Factor H Deficiency (OMIM# 609814)
Dense Deposit Disease (DDD, aka
Membranoproliferative Glomerulonephritis Type II, MPGNII)
Association studies have linked polymorphisms in the Factor H
gene (HF1, *134370)
with DDD (Abrera-Abeleda et al., 2005). DDD is a kidney disease
in which dense deposits form in the glomerular basement
membrane. The diagnosis is made on renal biopsy: electron
microscopy resolves the dense deposit, and immunofluoresence
will be positive for C3 and negative for immunoglobulins.
Atypical
Hemolytic-Uremic Syndrome
The clinical manifestations of hemolytic-uremic syndrome (HUS; 235400) include
hemolytic anemia, thrombocytopenia and acute renal failure.
Most cases are associated with epidemics of diarrhea caused by
verocytotoxin-producing bacteria [Escherichia
coli O157:H7
(Stx-HUS)].
Atypical hemolytic uremic syndrome (aHUS) is a
rarer disease. It is not associated with Stx-HUS infection and
neither does it present with watery, bloody diarrhea (Warwicker
et all, 1997). It can be either sporadic or familial and has an
extremely unfavorable prognosis, with about 50% of persons
progressing to ESRD and 25% dying during the acute illness;
transplantation in many survivors is unsuccessful (Schieppati et
al., 1992; Taylor et al., 2004). Genetics studies have shown
that approximately 50% of cases of aHUS are caused by mutations
in MCP, CFH and IF(Caprioli
et al., 2006). Identifying the genetic cause of aHUS is
extremely important as it can help to direct clinical treatment
decisions.
Complement Factor H( HF1, *134370)
Complement
Factor H is a serum glycoprotein that controls function of the
alternative pathway (AP) of the complement cascade. It acts as
a cofactor for factor I (IF; 217030)
and regulators the AP C3 convertase in the fluid phase and on
surfaces like the glomerular basement membrane in the kidney and
Bruch’s membrane in the eye. The HF1 gene contains
22 exons and encodes the 1231 amino acid protein Complement
Factor H.
MORL screening methodology
Oligonucleotide primers have been designed to amplify each exon
of HF1.
Because HF1 contains
many non-disease causing polymorphisms, it is sequenced directly
using overlapping primer sets.
Sensitivity
Sensitivity is greater than 99%.
Turn-around time
Turn around time is approximately 3 months.
Cost: $700
Indications for screening
Screening is offered to persons with aHUS and biopsy-proven DDD;
we will also offer screening for some other factor H-related
diseases.
Web sites
Kidneeds (not-for-profit
foundation dedicated to the cure of DDD)www.medicine.uiowa.edu/kidneeds
Foundation for Children with Atypical HUS
http://www.atypicalhus.50megs.com/index.html
References
Abrera-Abeleda, M.A. et al.: Variations
in the Complement Regulatory Genes Factor H (CFH) and Factor H
Related 5 (CFHR5) are Associated with Membranoproliferative
Glomerulonephritis Type II (Dense Deposit Disease).
J Med Genet. 2005 Nov 18; [Epub ahead of print]
PubMed ID: 16299065
PubMed Search
Caprioli, J.
et al.: Genetics
of HUS: the impact of MCP, CFH, and IF mutations on clinical
presentation, response to treatment, and outcome. Blood.
108(4):1267-79, 2006. Epub 2006 Apr 18.
PubMed ID: 16621965
PubMed Search
Schieppati, A. et al.: Renal
function at hospital admission as a prognostic factor in adult
hemolytic uremic syndrome. The Italian Registry of Haemolytic
Uremic Syndrome. Am Soc Nephrol. 2(11):1640-4, 1992.
PubMed ID: 1610985
PubMed Search
Taylor, C.M. et al.: Clinico-pathological
findings in diarrhoea-negative haemolytic uraemic syndrome. Pediatr
Nephrol.19(4): 419-25, 2004. Epub 2004 Feb 24
PubMed ID: 14986082
PubMed Search
Warwicker,
P. et al.: Genetic
studies into inherited and sporadic hemolytic uremic syndrome. Kidney
Int. 53:
836-844, 1998.
PubMed ID : 9551389
