Four novel connexin 32 mutations in X-linked Charcot-Marie-Tooth disease. Phenotypic variability and central nervous system involvement.
Charcot-Marie-Tooth (CMT) disease, the most common hereditary neuropathy, is clinically and genetically heterogeneous. X-linked CMT (CMTX) is usually caused by mutations in the gap junction protein b 1 gene (GJB1) coding for connexin 32 (Cx32). The clinical manifestations of CMTX are characterized by significant variability, with some patients exhibiting central nervous system (CNS) involvement. We report four novel mutations in GJB1, c.191G>A (p.Cys64Tyr), c.508G>T (p.Val170Phe), c.778A>G (p.Lys260Glu) and c.300C>G (p.His100Gln) identified in four unrelated Greek families. These mutations were characterized by variable phenotypic expression, including a family with the Roussy-Lévy syndrome, and three of them were associated with mild clinical CNS manifestations.
Neurogenetics Unit, 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece. Electronic address: gkaradim@med.uoa.gr.
Georgia
G
Karadima
Neurogenetics Unit, 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece.
Georgios
G
Koutsis
Neurogenetics Unit, 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece.
Maria
M
Raftopoulou
Neurogenetics Unit, 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece.
Paraskewi
P
Floroskufi
Neurogenetics Unit, 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece.
Karolina-Maria
KM
Karletidi
Neurogenetics Unit, 1st Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece.
Marios
M
Panas
D000293:Adolescent; D000328:Adult; D002490:Central Nervous System / Q000473:pathology*; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology*; D017630:Connexins / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D000097002:Gap Junction beta-1 Protein
CMTX; CNS involvement; Charcot- Marie- Tooth; Connexin 32; GJB1; Mutation