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Palmoplantar keratoderma and Charcot–Marie–Tooth disease: combination of two independent genetic diseases? Identification of two point mutations in the MPZ and KRT 1 genes by whole‐exome sequencing
Author(s) -
Gagliardi S.,
Ricca I.,
Ferrarini A.,
Valente M.,
Grieco G.S.,
Piccolo G.,
Alfonsi E.,
Delledonne M.,
Cereda C.
Publication year - 2017
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.15066
Subject(s) - exome sequencing , keratoderma , palmoplantar keratoderma , genetics , gene , identification (biology) , mutation , tooth disease , point mutation , medicine , biology , dermatology , hyperkeratosis , botany
In the eighties a clinical and familiar condition in which two different diseases Charcot-Marie-Tooth Disease type 2 (CMT2), and Palmoplantar Keratoderma (PPK) seemed to define an interesting complex phenotype (OMIM 148360) has been described. The regular association of this phenotype and the autosomal dominant trait has suggested that this clinical condition was expression of the same mutant gene. Exome analysis has been performed in an Italian family which members were affected by CMT2, PPK and CMT/PPK.Genetic analysis showed the presence of a non-synonymous mutation Ser44Phe in myelin protein zero (MPZ) gene in subject affected by CMT2 disease, moreover we detected a new mutation Phe200Leu in Keratin 1 (KRT1) gene in patients affected by PPK. The patients with CMT2/PPK phenotype were carriers of both mutations (S44P/F200L). These mutations were absent in a healthy family member.Exome by Next Generation Sequencing (NGS) data suggest that the complex phenotype described results from the combined effect of two point mutations in CMT2 and PPK genes. In fact, the clinical condition is a consequence of combination of two heterozygous mutations in different genes and not in a common mutant one. This article is protected by copyright. All rights reserved.