This innovation is related to methods for screening patients for autosomal recessive hypophosphatemic rickets (ARHR) resulting from defective Dentin Matrix Protein 1 (DMP1) expression. These methods are used to genetically screen patients for the presence of defects in the (DMP1) to diagnose the existence of, or assess the risk of producing offspring from those who suffer from ARHR.

One method relates to detecting individuals that express a defective DMP1 protein. Such individuals may exhibit ARHR or they may be carriers of the disease. This method involves sequencing either a portion of, or the entire length of the DMP1 gene isolated from the individual undergoing analysis to identify DMP1 variants. More particularly, the patient's DMP1 sequences are screened to detect a DMP1 variant that has a deletion of nucleic acid sequences 1484-1490 (deletion of CTATCAC; SEQ ID NO: 35) and the presence of the contiguous sequence CCAACTGTGAAGATC (SEQ ID NO: 36).

A second testing method utilizes a kit for screening biological samples for the presence of defective DMP1 genes. The kit is comprised of a set of PCR primers for amplifying the DMP1 gene, or alternatively the kit has one or more sets of PCR primers for amplifying one or more specific regions of the DMP1 gene. The kit may be further provided with reagents for conducting nucleic acid sequencing, one or more reagents for conducting PCR reactions, or labeled nucleic acid probes that specifically bind to defective DMP1 gene sequences relative to the native DMP1 sequence.

Another method described by this technology would detect aberrant DMP1 expression in a patient's cells, as a diagnostic indicator of ARHR. The method comprises contacting proteins of the patient's tissue with an ligand that specifically binds to the peptide of SEQ ID NO: 42 or SEQ ID NO: 43, detecting specific ligand-DMPl complexes, wherein the formation of ligand-DMP1 complexes indicates a risk of developing ARHR.

File Number: 07UMK097 

Web site: http://www.umkc.edu/ors/tt

Disease: Musculoskeletal Disorders