improved genetics testing for CMT 1A and HNPP from Australia

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Abstract from Hum Mutat. 2004 Aug;24(2):164-71.

Improved testing for CMT1A and HNPP using multiplex ligation-dependent

probe amplification (MLPA) with rapid DNA preparations: Comparison with

the interphase FISH Method.

Slater H, Bruno D, Ren H, La P, Burgess T, Hills L, Nouri S, Schouten J,

Andy Choo KH.

Genetic Health Services and Murdoch Childrens Research

Institute, University of Melbourne Department of Paediatrics, Royal

Children's Hospital, Parkville, Australia.

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.