title: Giant axonal neuropathy: clinical and genetic study in six cases.
abstract: BACKGROUND
  Giant axonal neuropathy (GAN) is a severe recessive disorder characterised by variable combination of progressive sensory motor neuropathy, central nervous system (CNS) involvement, and "frizzly" hair. The disease is caused by GAN gene mutations on chromosome 16q24.1.
  
  
  OBJECTIVE
  To search for GAN gene mutations in Turkish patients with GAN and characterise the phenotype associated with them.
  
  
  METHODS
  Linkage and mutation analyses were performed in six affected patients from three consanguineous families. These patients were also investigated by cranial magnetic resonance imaging (MRI) and electroencephalography (EEG). Electromyography (EMG) was performed in heterozygous carriers from family 1 and family 3.
  
  
  RESULTS
  Linkage to 16q24.1 was confirmed by haplotype analysis. GAN mutations were identified in all families. Family 1 had the R293X mutation, previously reported in another Turkish family. Families 2 and 3, originating from close geographical areas, shared a novel mutation, 1502+1G>T, at the donor splice site of exon 9. All patients displayed a common phenotype, including peripheral neuropathy, cerebellar ataxia, and frizzly hair. Cranial MRI showed diffuse white matter abnormalities in two patients from family 1 and the patient from family 3, and minimal white matter involvement in the patient from family 2. EMG of a heterozygous R293X mutation carrier showed signs of mild axonal neuropathy, whereas a 1502+1G>T mutation carrier had normal EMG. EEG abnormalities were found in three patients.
  
  
  CONCLUSIONS
  These findings highlight the association of CNS involvement, in particular white matter abnormalities, with peripheral neuropathy in GAN. The phenotypical consequences of both mutations (when homozygous) were similar.
authors.affiliation: Hacettepe Cocuk Hastahanesi, Cocuk Noroloji Bolumu, 06100, Ankara, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Demir
authors.forename: P
authors.initials: P
authors.lastname: Bomont
authors.forename: S
authors.initials: S
authors.lastname: Erdem
authors.forename: L
authors.initials: L
authors.lastname: Cavalier
authors.forename: M
authors.initials: M
authors.lastname: Demirci
authors.forename: G
authors.initials: G
authors.lastname: Kose
authors.forename: S
authors.initials: S
authors.lastname: Muftuoglu
authors.forename: A N
authors.initials: AN
authors.lastname: Cakar
authors.forename: E
authors.initials: E
authors.lastname: Tan
authors.forename: S
authors.initials: S
authors.lastname: Aysun
authors.forename: M
authors.initials: M
authors.lastname: Topcu
authors.forename: P
authors.initials: P
authors.lastname: Guicheney
authors.forename: M
authors.initials: M
authors.lastname: Koenig
authors.forename: H
authors.initials: H
authors.lastname: Topaloglu
mesh_terms: D000293:Adolescent; D001369:Axons / Q000473:pathology*; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D004252:DNA Mutational Analysis; D003711:Demyelinating Diseases / Q000235:genetics* / Q000473:pathology*; D004569:Electroencephalography; D004576:Electromyography; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D012867:Skin / Q000473:pathology; D013497:Sural Nerve / Q000473:pathology