title: 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.
abstract: 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.
authors.affiliation: DNA Laboratory, Department of Child Neurology, Charles University 2nd Medical School and University Hospital Motol, Prague, Czech Republic. dana.brozkova@seznam.cz
authors.forename: Dana
authors.initials: D
authors.lastname: Safka Brožková
authors.forename: Soňa
authors.initials: S
authors.lastname: Nevšímalová
authors.forename: Radim
authors.initials: R
authors.lastname: Mazanec
authors.forename: Bernd
authors.initials: B
authors.lastname: Rautenstrauss
authors.forename: Pavel
authors.initials: P
authors.lastname: Seeman
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000208:ethnology* / Q000235:genetics*; D018153:Czech Republic; D051767:Early Growth Response Protein 2 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012720:Severity of Illness Index
chemical_list: C497326:EGR2 protein, human; D051767:Early Growth Response Protein 2