Improved testing for CMT1A and HNPP using multiplex ligation-dependent probe amplification (MLPA) with rapid DNA preparations: Comparison with the interphase FISH Method
- 1 August 2004
- journal article
- research article
- Published by Hindawi Limited in Human Mutation
- Vol. 24 (2), 164-171
- https://doi.org/10.1002/humu.20072
Abstract
Charcot‐Marie‐Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are the two most common peripheral neuropathies, with incidences of about 1 in 2,500. Several techniques can be used to detect the typical 1.5‐Mb duplication or deletion associated with these respective conditions, but none combines simplicity with high sensitivity. MLPA is a new technique for measuring sequence dosage. We have assessed its performance for the detection of the specific 1.5‐Mb duplication/deletion by prospectively testing 50 patients referred with differential diagnoses of CMT or HNPP. Probes were designed to evaluate the TEKT3, PMP22, and COX10 genes within the CMT1A/HNPP region. We have compared the results with our existing fluorescence in situ hybridization (FISH) assay, which was performed in parallel. There was concordance of results for 49 patients. Of note, one patient showed an intermediate multiplex ligation‐dependent probe amplification (MLPA) result with an abnormal FISH result, which is consistent with mosaicism. The assay works equally well with either purified DNA or rapid DNA preparations made by direct cell lysis. The use of the latter significantly reduces the cost of the assay. MLPA is a sensitive, specific, robust, and cost‐effective technique suitable for fast, high‐throughput testing and offers distinct advantages over other testing methods. Hum Mutat 24:164–171, 2004.Keywords
This publication has 19 references indexed in Scilit:
- A Rapid and Definitive Test for Charcot-Marie-Tooth 1A and Hereditary Neuropathy with Liability to Pressure Palsies Using Multiplexed Real-Time PCRGenetic Testing, 2003
- Rapid detection of 17p11.2 rearrangements by FISH without cell culture (direct FISH, DFISH): A prospective study of 130 patients with inherited peripheral neuropathiesAmerican Journal of Medical Genetics Part A, 2003
- Charcot-Marie-Tooth disease and sleep apnoea syndrome: a family studyThe Lancet, 2001
- Real-time quantitative polymerase chain reactionHuman Genetics, 2000
- Charcot-Marie-Tooth Polyneuropathy: Duplication, Gene Dosage, and Genetic HeterogeneityPediatric Research, 1999
- Polymorphisms in the PMP-22 gene region (17p11.2-12) are crucial for simplified diagnosis of duplications/deletionsHuman Genetics, 1997
- Mosaicism for the Charcot-Marie-Tooth disease type 1A duplication suggests somatic reversionHuman Genetics, 1996
- DNA deletion associated with hereditary neuropathy with liability to pressure palsiesCell, 1993
- Charcot–Marie–Tooth type 1A duplication appears to arise from recombination at repeat sequences flanking the 1.5 Mb monomer unitNature Genetics, 1992
- DNA duplication associated with Charcot-Marie-Tooth disease type 1ACell, 1991