title: A novel locus for a hereditary recurrent neuropathy on chromosome 21q21.
abstract: Hereditary recurrent neuropathies are uncommon. Disorders with a known molecular basis falling within this group include hereditary neuropathy with liability to pressure palsies (HNPP) due to the deletion of the PMP22 gene or to mutations in this same gene, and hereditary neuralgic amyotrophy (HNA) caused by mutations in the SEPT9 gene. We report a three-generation family presenting a hereditary recurrent neuropathy without pathological changes in either PMP22 or SEPT9 genes. We performed a genome-wide mapping, which yielded a locus of 12.4 Mb on chromosome 21q21. The constructed haplotype fully segregated with the disease and we found significant evidence of linkage. After mutational screening of genes located within this locus, encoding for proteins and microRNAs, as well as analysis of large deletions/insertions, we identified 71 benign polymorphisms. Our findings suggest a novel genetic locus for a recurrent hereditary neuropathy of which the molecular defect remains elusive. Our results further underscore the clinical and genetic heterogeneity of this group of neuropathies.
authors.affiliation: Program in Rare and Genetic Diseases, Centro de Investigación Príncipe Felipe (CIPF), CIPF and IBV-CSIC Associated Unit at CIPF, Valencia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Calpena
authors.affiliation: Program in Rare and Genetic Diseases, Centro de Investigación Príncipe Felipe (CIPF), CIPF and IBV-CSIC Associated Unit at CIPF, Valencia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Martínez-Rubio
authors.affiliation: Neurology Department, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Arpa
authors.affiliation: Pediatric Neurology Department, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: García-Peñas
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain; Program in Computational Medicine, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Montaner
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain; Program in Computational Medicine, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Dopazo
authors.affiliation: Program in Rare and Genetic Diseases, Centro de Investigación Príncipe Felipe (CIPF), CIPF and IBV-CSIC Associated Unit at CIPF, Valencia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Palau
authors.affiliation: Program in Rare and Genetic Diseases, Centro de Investigación Príncipe Felipe (CIPF), CIPF and IBV-CSIC Associated Unit at CIPF, Valencia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain. Electronic address: cespinos@cipf.es.
authors.forename: C
authors.initials: C
authors.lastname: Espinós
mesh_terms: D000293:Adolescent; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D004252:DNA Mutational Analysis; D005190:Family; D056426:Genetic Loci; D006239:Haplotypes; D006801:Humans; D008297:Male; D009185:Myelin Proteins / Q000235:genetics; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000503:physiopathology; D011110:Polymorphism, Genetic; D058112:Septins / Q000235:genetics
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human; C474315:SEPTIN9 protein, human; D058112:Septins
keywords: Genetic locus; Genome-wide mapping; Hereditary neuralgic amyotrophy; Hereditary recurrent neuropathy; SEPT9