Method of diagnosis of complement-mediated thrombotic microangiopathies
A method for identifying a patient's risk for developing complement-mediated thrombic microangiopathy is described. A sample of genetic material is obtained from a patient. The genetic material is amplified using primers specific for complement-mediated thrombic microangiopathy. After amplification, the genetic sequence of the amplicon is determined. The genetic sequence of the amplicon is compared to a reference sequence, and variations are identified between the sample amplicon and the reference sequence. A variation between the sample amplicon and the reference sequence is indicative of a risk for the patient for developing complement-mediated thrombic microangiopathy.
1. A method for determining a patient's risk for developing atypical hemolytic uremic syndrome (aHUS), the method comprising:
(a) detecting a DNA sequence alteration in a group of aHUS genes, the group consisting of: Complement factor H (CFH), Membrane cofactor protein (CD46), Complement factor 1 (CF1), Complement component 3 (C3), Complement factor B (CFB), Complement factor H-related protein 1 (CDHR1), Complement factor H-related protein 3 (CFHR3), Complement factor H-related protein 4 (CFHR4), Complement factor H-related protein 5 (CFHR5), Thrombomodulin (THBD), Plasminogen (PLG), and Diacyl glycerol kinase (DGKE), wherein the DNA sequence alteration is detected by analyzing the DNA sequence of the twelve aHUS genes in a sample, wherein the aHUS genes are analyzed by amplifying the twelve aHUS genes in the sample using a minimum of twenty four sequences selected from the group comprising SEQ ID NO. 1 through SEQ ID NO. 1014;
(b) comparing the amplified aHUS genes from step (a) with amplified aHUS sequences from a normal control subject; and
(c) determining the patient's risk for developing aHUS, wherein one or more DNA sequence alterations of CFH, CD46, CFI, C3, CFB, CFHR1, CFHR3, CFHR4, CFHR5, THBD, PLG, and DGKE in the sample that are not present in the normal control has a risk of developing aHUS.
2. The method of claim 1 wherein the aHUS genes comprise aHUS RNA from a sample or aHUS CDNA made from mRNA from the sample.
3. The method of claim 1 , wherein the DNA sequence alteration in the aHUS gene is a mutation.
4. The method of claim 1 , wherein the DNA sequence alteration in the aHUS gene is a deletion.
5. The method of claim 1 , wherein determining the patient's risk for developing aHUS is made within 48 hours of receipt of the sample from the patient.
6. The method of claim 1 , wherein determining the patient's risk for developing aHUS is made within 5 days of receipt of the sample from the patient.