New Technique in Diagnosis CMT1A and HNPP - from France

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Abstract from Am J Med Genet 2003 Apr 1;118A(1):43-8

Rapid detection of 17p11.2 rearrangements by FISH without cell culture

(direct FISH, DFISH): A prospective study of 130 patients with inherited

peripheral neuropathies.

Ravise N, Dubourg O, Tardieu S, Aurias F, Mercadiel M, Coullin P, Ruberg

M, Catala M, Lesourd S, Brice A, LeGuern E. INSERM U289, Hopital

Pitie-Salpetriere, Paris, France.

Charcot-Marie-Tooth (CMT) disease and hereditary neuropathy with

pressure palsies (HNPP) are two frequent hereditary motor and sensory

neuropathies. CMT is characterized by slowly progressive weakness and

atrophy, primarily in peroneal and distal leg muscles. The most frequent

form, CMT1A, is due, in most cases, to the duplication of a 1.5 Mb

region on chromosome 17p11.2 containing the peripheral myelin protein 22

gene (PMP22). The phenotype seems to result from dosage of the PMP22

gene.

This hypothesis is reinforced by the existence of HNPP, which is

clinically characterized by various recurrent truncular palsies or

sensory loss precipitated by minor trauma, which is caused by deletion

of the same 1.5 Mb region in 17p11.2. In clinical practice, the

detection of the duplication or the deletion in 17p11.2, which permits a

positive diagnosis, is still performed by time consuming methods

(Southern blot or various combinations of molecular tools). We developed

a method for the

rapid detection of 17p11.2 rearrangements, using " direct FISH " and PRINS

analyses, which does not require cell culture. In a prospective study of

92 patients with CMT and 38 with suspected HNPP, we compared this new

technique to classical strategies like Southern blot. The results

demonstrate the high sensitivity and specificity of the new FISH

technique for the diagnosis of CMT1A and HNPP. Moreover, because of its

simplicity and rapidity, this technique provides a useful alternative to

the molecular approaches that have been used to diagnose segmental

aneusomies, especially in the case of duplications that often go

undetected. Copyright 2003 Wiley-Liss, Inc.