Abstrakt
The LMNA gene was sequenced in 98 Czech patients from 94 unrelated families with early-onset axonal Charcot-Marie-Tooth (CMT) disease consistent with both autosomal recessive inheritance and sporadic cases. Biallelic pathogenic mutations were not found in any patient in this group.
One patient carried the c.1870CT mutation that is predicted to result in the amino-acid substitution, p. Arg624Cys, on one allele, but the second causative mutation was not detected.
LMNA mutation is not likely to be associated with the disease in this family. To exclude larger deletions/duplications in the LMNA gene not detectable by sequencing, 48 patients from this group were also analyzed with multiplex ligation-dependent probe amplification.
No rearrangements in the LMNA gene were detected. We conclude that mutations in the LMNA gene are absent from a large group of Czech patients with axonal autosomal recessive CMT disease.
Consequently, LMNA mutation screening does not seem to be relevant for axonal CMT DNA diagnostics. A similar situation may apply to other European populations.