Clinical and molecular analysis of X-linked Charcot-Marie-Tooth disease type 1 in Spanish population

• Published in: Clinical genetics 2006-12, Vol.70 (6), p.516-523
• Main Authors: Casasnovas, C, Banchs, I, Corral, J, Martínez-Matos, JA, Volpini, V
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Biological and medical sciences; Charcot-Marie-Tooth; Charcot-Marie-Tooth Disease - genetics; CMT X; Connexin 32; Connexins - genetics; Cx32; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Electrophysiology; Female; Fundamental and applied biological sciences. Psychology; Gap Junction beta-1 Protein; General aspects. Genetic counseling; Genetic Diseases, X-Linked - genetics; Genetic Diseases, X-Linked - pathology; Genetics of eukaryotes. Biological and molecular evolution; GJB1; Humans; Inheritance Patterns; Male; Medical genetics; Medical sciences; Molecular and cellular biology; Molecular Sequence Data; Mutation - genetics; Neurology; Pedigree; Phenotype; Polymorphism, Single-Stranded Conformational; Protein Conformation; Sequence Alignment; Sequence Analysis, DNA; Spain; X-linked CMT
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2006.00724.x

From 1995 to 2004, 979 families with hereditary peripheral neuropathy were referred to the Genetic Diagnosis Center. Using single‐strand conformation analysis (SSCA), the connexin 32 gene was analysed in all the patients from 498 families with sporadic or dominant inheritance with no male‐to‐male transmission and absence of the 17p2 duplication or deletion. Affected males had pes cavus, distal leg weakness, muscular distal atrophy, areflexia and distal sensory loss. The 106 families in which SSCA revealed abnormal migration electrophoresis were directly sequenced. We found 34 families (59 patients) with mutations in connexin 32 gene. In electrophysiological studies, 58.8% families presented slow and 14.7% intermediate nerve conduction velocities. Molecular findings revealed that codon 164 (29.4 ± 15.3%) and the second extracellular (EC2) domain (44.1 ± 16.6%) were the most frequently affected codon and domain of the connexin 32. Six novel mutations, Leu39fs, Glu47Gly, His153fs, Cys179Tyr, Cys201Phe and Ser211fs, were found in our study.