title: X-linked Charcot-Marie-Tooth type 1: stroke-like presentation of a novel GJB1 mutation.
abstract: X-linked Charcot-Marie-Tooth type 1 (CMTX1) is the second most common type of CMT and is caused by mutations in the Gap-Junction Beta-1 gene (GJB1), encoding connexin 32 which is expressed in Schwann cells as well as in oligodendrocytes. More than 400 GJB1 mutations have been described to date. Many mutation-carrier males have subclinical central nervous system (CNS) involvement, a few show mild CNS clinical signs, whereas only rarely overt though transient CNS dysfunction occurs. We report a 29-year-old man with CMTX1 who, at 16 years, showed short-lived CNS symptoms with transitory white matter abnormalities on cerebral magnetic resonance imaging (MRI) as first clinical presentation of a novel GJB1 mutation (p.Gln99_His100insGln). He had three consecutive episodes of right hemiparesis, together with sensory loss in the paretic limbs and expressive aphasia, all lasting a few hours, over a 2-day period, with concurrent white matter hyperintensity on MRI. These "stroke-like" episodes occurred just after arriving at sea level, after travelling from home at 700 m of altitude. Only a few years later did symptoms of peripheral neuropathy appear. In conclusion, CMTX1 should be included in the differential diagnosis of diseases characterized by transient CNS symptoms and white matter abnormalities on MRI.
authors.affiliation: Clinic of Central and Peripheral Degenerative Neuropathies Unit, Department of Clinical Neurosciences, IRCCS Foundation, "C. Besta" Neurological Institute, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sagnelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Piscosquito
authors.forename: Luisa
authors.initials: L
authors.lastname: Chiapparini
authors.forename: Claudia
authors.initials: C
authors.lastname: Ciano
authors.forename: Ettore
authors.initials: E
authors.lastname: Salsano
authors.forename: Paola
authors.initials: P
authors.lastname: Saveri
authors.forename: Micaela
authors.initials: M
authors.lastname: Milani
authors.forename: Franco
authors.initials: F
authors.lastname: Taroni
authors.forename: Davide
authors.initials: D
authors.lastname: Pareyson
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology*; D017630:Connexins / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D020521:Stroke / Q000503:physiopathology*; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D000097002:Gap Junction beta-1 Protein
keywords: GJB1 gene; X-linked Charcot-Marie-Tooth disease; central nervous system symptoms; connexin 32; magnetic resonance imaging