Clinical and molecular study of Charcot-Marie-Tooth disease in a Galician Gypsy

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(Oral presentation at Antwerp Consortium July 2009)

Clinical and molecular study of Charcot-Marie-Tooth disease in a Galician Gypsy

family.

C.Concheiro-Alvarezl ,P. Blanco-Ariasl ,2, J. Pardo3 , I. Requena3

, M. Arias3 , A. Carracedol,2,4 and M.J. Sobrido2 ,4

lGrupo de Medicina Xen6mica, Universidad de Santiago de Compostela, Santiago de

Compostela, Spain; 'Centro para Investigacion en Red de Enfermedades Raras

(CIBERER), ISCIII, Spain; 3Servicio de Neurologia,

Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain;

4Pundacion Publica Galega de Medicina Xenomica, Santiago de Compostela, Spain

Charcot-Marie-Tooth disease (CMT) is a hereditary motor and sensory neuropathy

which represents the most common inherited neurological disorder (approximately

one in 2500 individuals) CMT is genetically and clinically heterogeneous and

affects individuals of all

ethnic backgrounds.

A large consanguineous gypsy family with at least 14 patients diagnosed with an

early onset demyelinating polyneuropathy was studied. Ten out of sixteen

individuals clinically characterized presented definitive symptoms of CMT

disease One of the patients, a woman with three affected offspring, presented

very mild symptoms compared to her children. The pattern of transmission

suggests an autosomal recessive inheritance.

We carried out the following genetic analyses: 1) a SNP-genotyping-based test

for the duplication of a chromosomal segment containing PMP22 (the most frequent

molecular alteration in

demyelinating CMT), 2) systematic sequencing of the coding region and

exon-intron junctions ofPMP22, MPZ, GDAPl, NEFL, GIBl, LlTAFISIMPLE, EGR2, LMNA,

MFN2, RAB7, HSPBl and HSPB8 and, 3) sequencing screening of specific mutations

previously identified in Gypsies in PRX, SH3TC2 and NDRG1.

Conclusion: our data support that the kindred described herein has an early

onset, autosomal-recessive, demyelinating CMT and that it is not due to any of

the most frequent alterations causing CMT or to specific mutations associated to

CMT in Gypsies. The pedigree offers enough statistical power to identify the

causal region by linkage analysis.