title: Three novel mutations and genetic epidemiology analysis of the Gap Junction Beta 1 (GJB1) gene among Hungarian Charcot-Marie-Tooth disease patients.
abstract: Pathogenic variants of the gap junction beta 1 (GJB1) gene are responsible for the Charcot-Marie-Tooth neuropathy X type 1 (CMTX1). In this study, we report the mutation frequency of GJB1 in 210 Hungarian CMT patients and the phenotype comparison between male and female CMTX1 patients. Altogether, 13 missense substitutions were found in the GJB1 gene. Among them, 10 have been previously described as pathogenic variants (p.Arg15Trp, p.Val63Ile, p.Leu89Val, p.Ala96Gly, p.Arg107Trp, p.Arg142Gln, p.Arg164Trp, p.Arg164Gln, p.Pro172Ala and p.Asn205Ser), while 3 were novel, likely pathogenic alterations (p.Val13Glu, p.Glu186Gly, p.Met194Ile). These variants were not present in controls and were predicted as disease causing by in silico analysis. The frequency of the variants was 6.7% in our cohort which refers to a common cause of hereditary neuropathy among Hungarian patients. In addition to the classical phenotype, CNS involvement was proved in 26.1% of the CMTX1 patients. GJB1 pathogenic alterations were found mainly in males but we also detected them in female probands. The statistical analysis of CMTX1 patients revealed a significant difference between the two genders regarding the age of onset, Charcot-Marie-Tooth neuropathy and examination scores.
authors.affiliation: Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary.
authors.forename: Gyorgy Mate
authors.initials: GM
authors.lastname: Milley
authors.affiliation: Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary; Department of Neurology, University of Szeged, Szeged, Hungary.
authors.forename: Edina Timea
authors.initials: ET
authors.lastname: Varga
authors.affiliation: Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Grosz
authors.affiliation: Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bereznai
authors.affiliation: MTA-SE NAP B Peripheral Nervous System Research Group, Dept. of Neurology, Semmelweis University, Budapest, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Aranyi
authors.affiliation: Department of Neurology, Medical Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Boczan
authors.affiliation: Department of Neurology, Andras Josa Teaching Hospital, Nyiregyhaza, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Dioszeghy
authors.affiliation: University of Pecs, Faculty of Health Sciences, Pecs and Molecular Pathology, Markusovszky University Teaching Hospital, Szombathely, Hungary.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Kálmán
authors.affiliation: Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary.
authors.forename: Aniko
authors.initials: A
authors.lastname: Gal
authors.affiliation: Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary. Electronic address: molnarmj@gmail.com.
authors.forename: Maria Judit
authors.initials: MJ
authors.lastname: Molnar
mesh_terms: D000328:Adult; D017668:Age of Onset; D002607:Charcot-Marie-Tooth Disease / Q000453:epidemiology* / Q000235:genetics*; D015331:Cohort Studies; D017630:Connexins / Q000235:genetics*; D005260:Female; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D012720:Severity of Illness Index; D012737:Sex Factors; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D000097002:Gap Junction beta-1 Protein
keywords: CMTX1; Charcot-Marie-Tooth; Connexin 32; Gap junction beta 1