title: Molecular and clinical delineation of 12 patients with glycogen storage disease type III in Western Turkey.
abstract: BACKGROUND
  Glycogen storage disease type III (GSD III; MIM #232400) is an autosomal recessive inherited disorder characterized by fasting hypoglycemia, growth retardation, hepatomegaly, progressive myopathy, and cardiomyopathy. GSD III is caused by deficiency in the glycogen debranching enzyme (gene symbol: AGL). Molecular analyses of AGL have indicated heterogeneity depending on ethnic groups. In Turkey we reported 13 different AGL mutations from GSD III patients in the Eastern region; however, the full spectrum of AGL mutations in Turkish population remains unclear. Here we investigated 12 GSD III patients mostly from Western Turkey.
  
  
  METHODS
  The full coding exons, their relevant exon-intron boundaries, and the 5'- and 3'-flanking regions of the patients' AGL were sequenced. AGL haplotypes were determined. Splicing mutations were characterized by RNA transcript analysis.
  
  
  RESULTS
  Twelve different mutations were identified: 7 novel AGL mutations [69-base pair deletion (c.1056_1082+42del69), 21-base par deletion (c.3940_3949+11del21), two small duplications (c.364_365dupCT and c.1497_1500dupAGAG), and 3 splicing mutations (c.1736-11A>G, c.3259+1G>A and c.3588+2T>G)], along with 5 known mutations (c.1019delA, c.958+1G>A, c.4161+5G>A, p.R864X and p.R1218X). Transcripts of splicing mutations (c.1736-11A>G, c.3588+2T>G and c.4161+5G>A) were shown to cause aberrant splicing. AGL haplotype analyses suggested that c.1019delA and c.958+1G>A are founder mutations in Turkish patients, while p.R864X is a recurrent mutation.
  
  
  CONCLUSIONS
  Our study broadens the spectrum of AGL mutations and demonstrates that mutations in Western Turkey are different from those in the Eastern region.
authors.affiliation: Okinaka Memorial Institute for Medical Research, Tokyo, Japan; Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan. Electronic address: QFG00550@nifty.com.
authors.forename: Minoru
authors.initials: M
authors.lastname: Okubo
authors.affiliation: Department of Pediatric Metabolism and Nutrition, Ege University Medical Faculty, Izmir, Turkey.
authors.forename: Sema Kalkan
authors.initials: SK
authors.lastname: Ucar
authors.affiliation: Molecular Genetics and Metabolism Laboratory, Munich, Germany.
authors.forename: Teodor
authors.initials: T
authors.lastname: Podskarbi
authors.affiliation: Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Murase
authors.affiliation: Molecular Genetics and Metabolism Laboratory, Munich, Germany.
authors.forename: Yoon S
authors.initials: YS
authors.lastname: Shin
authors.affiliation: Department of Pediatric Metabolism and Nutrition, Ege University Medical Faculty, Izmir, Turkey.
authors.forename: Mahmut
authors.initials: M
authors.lastname: Coker
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006010:Glycogen Storage Disease Type III / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D017422:Sequence Analysis, DNA; D014421:Turkey; D055815:Young Adult
keywords: AGL; Aberrant splicing; Glycogen storage disease type III; Haplotype; Mutation; Turkey