title: Charcot-Marie-Tooth disease type I and related demyelinating neuropathies: Mutation analysis in a large cohort of Italian families.
abstract: Charcot-Marie-Tooth neuropathy type 1 (CMT1), the most common hereditary neurological disorder in humans, is characterized by clinical and genetic heterogeneity. It is caused mainly by a 1.5 Mb duplication in 17p11.2, but also by mutations in the myelin genes PMP22 (peripheral myelin protein 22), MPZ (myelin protein zero), Cx32 (connexin 32; also called GJB1), and EGR2 (early growth response 2). In this study, we have screened 172 index cases of Italian families in which there was at least one subject with a CMT1 diagnosis for the duplication on 17p11.2 and mutations in these genes. Among 170 informative unrelated patients, the overall duplication frequency was 57.6%. A difference could be observed between the duplication frequency in familial cases (71.6%) and that observed in non-familial cases (36.8%). Among the non-duplicated patients, 12 were mutated in Cx32, four in MPZ, two in PMP22, and none in the EGR2. In the non-duplicated cases, the overall point mutation frequency for these genes was 25.0%. We describe the mutations identified, and consider possible genotype-phenotype correlation.
authors: Laboratorio di Genetica Umana, Dipartimento di Biologia, Università di Padova, Padova, Italy. mlsmst@civ.bio.unipd.it
authors: M L
authors: ML
authors: Mostacciuolo
authors: E
authors: E
authors: Righetti
authors: M
authors: M
authors: Zortea
authors: V
authors: V
authors: Bosello
authors: F
authors: F
authors: Schiavon
authors: L
authors: L
authors: Vallo
authors: L
authors: L
authors: Merlini
authors: G
authors: G
authors: Siciliano
authors: G M
authors: GM
authors: Fabrizi
authors: N
authors: N
authors: Rizzuto
authors: M
authors: M
authors: Milani
authors: S
authors: S
authors: Baratta
authors: F
authors: F
authors: Taroni
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000145:classification / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D015331:Cohort Studies; D017630:Connexins / Q000235:genetics; D004252:DNA Mutational Analysis; D020440:Gene Duplication; D005787:Gene Frequency / Q000235:genetics; D020131:Genes, Duplicate / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics*; D006801:Humans; D007558:Italy; D009154:Mutation / Q000235:genetics*; D018993:Myelin P0 Protein / Q000235:genetics; D009185:Myelin Proteins / Q000235:genetics; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D018993:Myelin P0 Protein; D009185:Myelin Proteins; D000097002:Gap Junction beta-1 Protein; C073687:PMP22 protein, human