Thrombomodulin
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.

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 al., 1998).  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 may survivors is unsuccessful (Schieppati et al., 1992; Taylor et al., 2004).  Genetic studies have shown that approximately 50% of cases of aHUS are caused by mutations in MCP, CFH and CFI (Caprioli et al., 2006).  Identifying the genetic cause of aHUS is extremely important as it can help to direct clinical treatment decisions.

Thrombomodulin (THBD OMIM# +188040)
Thrombomodulin, a 575-amino-acid protein encoded by the gene THBD, is an endothelial-cell glycoprotein that is a negative regulator of the complement system.  It contains a lectin-like domain that suppresses leukocyte trafficking to prevent inflammation.  Mutations in THBD have been found in persons with aHUS.  The THBD gene contains 1 exon.

MORL screening methodology
Overlapping oligonucleotide primer sets have been designed to amplify the exon of THBD which are used for bi-directional sequencing.

Sensitivity
Sensitivity is greater than 99%.

Turn-around time
Turn around time is approximately 3 months.

Cost: $300

Indications for screening
Screening is offered to person with aHUS.

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
Delvaeye, M.; Noris, M.; De Vriese, A.; Esmon, C. T.; Esmon, N. L.; Ferrell, G.; Del-Favero, J.; Plaisance, S.; Claes, B.; Lambrechts, D.; Zoja, C.; Remuzzi, G.; Conway, E. M.:  Thrombomodulin mutations in atypical hemolytic-uremic syndrome. Proc. Nat. Acad. Sci. 82: 708-712, 19857.
PubMed ID:  19625716
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