RESUMO
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Assuntos
Doença de Charcot-Marie-Tooth/genética , Proteína P0 da Mielina/genética , Adulto , Sequência de Aminoácidos , Substituição de Aminoácidos , Sequência de Bases , Deleção Cromossômica , Cromossomos Humanos Par 1 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutagênese Insercional , Mutação de Sentido Incorreto , Mutação Puntual , Polimorfismo Conformacional de Fita Simples , Análise de Sequência de DNA , TurquiaRESUMO
The major Charcot- Marie-Tooth Type 1 (CMT1) locus, CMT1A, and Hereditary neuropathy with liability to pressure palsies (HNPP) cosegregate with a 1.5-Mb duplication and a 1.5-Mb deletion, respectively, in band 17p11.2. Point mutations in peripheral myelin gene 22 (PMP22), myelin protein zero (MPZ), and connexin 32 (Cx32) have been reported in CMT1, and in PMP22 in HNPP patients without deletion. We have screened 54 CMT1 patients, of variable clinical severity, and 25 HNPP patients from Turkey, with no duplication or deletion, for mutations in the PMP22 and Cx32 genes. A novel frameshift mutation affecting the second extracellular domain of PMP22 was found in an HNPP patient, while a point mutation in the second transmembrane domain of the protein was detected in a CMT1 patient. Two point mutations affecting different domains of Cx32 were identified in two CMTX patients. Another patient was found to carry a polymorphism in a non-conserved codon of the Cx32 gene. The clinical phenotypes of the patients correlate well with the effect of the mutation on the protein.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Conexinas/genética , Proteínas da Mielina/genética , Doenças do Sistema Nervoso Periférico/genética , Adolescente , Adulto , Criança , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Masculino , Fenótipo , Polimorfismo Genético , Turquia , Proteína beta-1 de Junções ComunicantesRESUMO
BACKGROUND: Charcot-Marie-Tooth disease type 2A (CMT2A) was assigned to a 19.3-cM region on chromosome 1p35-36. A missense mutation in the kinesin family member 1B gene (KIF1B) was reported in a single CMT2A family. OBJECTIVE: To report the clinical and genetic data of a Turkish family with CMT2A. METHODS: Linkage to CMT2 loci was investigated in the family. Haplotype analysis of the CMT2A region was completed using additional single-nucleotide polymorphism and short tandem repeat markers. The KIF1B gene was sequenced on genomic DNA and cDNA in two patients. RESULTS: A recombination event narrowed the CMT2A locus to a 9.3-cM region flanked by D1S160 and D1S434. No mutation in KIF1B was found. CONCLUSION: The exclusion of KIF1B gene mutations in this family suggests the involvement of another CMT2A gene in the linked region.