Charcot-Marie-Tooth neuropathy due to a novel EGR2 gene mutation with mild phenotype - Usefulness of human mapping chip linkage analysis in a Czech family

摘要

Charcot-Marie-Tooth neuropathies (CMT) are a group of clinically and genetically heterogeneous disorders of the peripheral nervous system. Selection of candidate disease genes for mutation analysis is sometimes difficult since more than 40 genes and loci are known to be associated with CMT neuropathies. Hence a Czech family Cz-CMT with demyelinating type of autosomal dominant CMT disease was investigated by genome-wide linkage analysis by means of single-nucleotide polymorphism (SNP) arrays. Among 35 regions with linkage, five carried known CMT genes. In the final result a novel . early growth response 2 - missense mutation c.1235 A>G, p.Glu412Gly was found. Surprisingly, the more severely affected proband carried an additional heterozygous . myelin protein zero variant p.Asp246Asn detected previously, which may modify the phenotype. However, this . MPZ variant is benign in heterozygous state alone, because it is also carried by the patient's healthy father.