title: HSPB1 and HSPB8 in inherited neuropathies: study of an Italian cohort of dHMN and CMT2 patients.
abstract: Mutations in the small heat-shock protein 27 kDa protein 1 (HSPB1) and 22 kDa protein 8 (HSPB8) genes were associated with distal hereditary motor neuropathy (dHMN) and with the axonal form of Charcot-Marie-Tooth disease type 2 (CMT2). Here we report the clinical and molecular evaluation of an Italian dHMN and CMT2 cohort to establish HSPB1 and HSPB8 mutation occurrence and associated clinical features. One hundred and sixty-seven patients with dHMN or CMT2 were studied. HSPB1 and HSPB8 exons 1 and 3 molecular analysis was carried out through DHPLC and direct sequencing of each variant chromatogram. HSPB8 exon 2 was analyzed by direct sequencing. Four mutations in five unrelated dHMN patients and four mutations in four unrelated CMT2 cases were found in HSPB1. The p.Arg136Leu mutation was found in two patients with different phenotypes. Electroneurographical follow-up study in a dHMN patient revealed that sensory impairment occurred with disease progression. The HSPB1 mutation frequency was 8% in dHMN and 4% in CMT2 patients. The significant HSPB1 mutation frequency in both phenotypes indicates its relevance in the pathogenesis of these neuropathies. Recent literature data suggest a continuum between dHMN and CMT2. We confirm this finding in our cohort, proposing a definite relationship between these disorders.
authors.affiliation: Department of Neuroscience, Ophthalmology and Genetics-Section of Medical Genetics, University of Genoa, Genoa, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Capponi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Geroldi
authors.forename: Paola
authors.initials: P
authors.lastname: Fossa
authors.forename: Marina
authors.initials: M
authors.lastname: Grandis
authors.forename: Paola
authors.initials: P
authors.lastname: Ciotti
authors.forename: Rossella
authors.initials: R
authors.lastname: Gulli
authors.forename: Angelo
authors.initials: A
authors.lastname: Schenone
authors.forename: Paola
authors.initials: P
authors.lastname: Mandich
authors.forename: Emilia
authors.initials: E
authors.lastname: Bellone
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000595:Amino Acid Sequence; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000235:genetics*; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; C413214:HSPB8 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D017346:Protein Serine-Threonine Kinases