Screening for mutations in a genetically heterogeneous disorder: DHPLC versus DNA sequence for mutation detection in multiple genes causing Charcot-Marie-Tooth neuropathy.

To determine the efficacy of denaturing high-performance liquid chromatography (DHPLC) for mutation detection in genetically heterogeneous diseases using Charcot-Marie-Tooth neuropathy as a model.,(1) Identification of the optimal conditions for mutation scanning by DHPLC using 50 known variants of PMP22, MPZ, GJB1 and EGR2. (2) Comparison of DHPLC with DNA sequencing for mutation detection in 168 patient DNA samples.,We established the optimal conditions for screening PMP22, MPZ, GJB1, and EGR2 for mutations. Under optimized conditions, DHPLC was as sensitive as DNA sequencing and detected two mutations that were not identified by automated DNA sequence.,DHPLC increases the efficiency and sensitivity of mutation screening in genetically heterogeneous diseases.