title: Spectrum of AGL mutations in Chinese patients with glycogen storage disease type III: identification of 31 novel mutations.
abstract: Glycogen storage disease type III (GSD III), a rare autosomal recessive disease characterized by hepatomegaly, fasting hypoglycemia, growth retardation, progressive myopathy and cardiomyopathy, is caused by deficiency of the glycogen debranching enzyme (AGL). Direct sequencing of human AGL cDNA and genomic DNA has enabled analysis of the underlying genetic defects responsible for GSD III. To date, the frequent mutations in different areas and populations have been described in Italy, Japan, Faroe Islands and Mediterranean area, whereas little has been performed in Chinese population. Here we report a sequencing-based mutation analysis in 43 Chinese patients with GSD III from 41 families. We identified 51 different mutations, including 15 splice-site (29.4%), 11 small deletions (21.6%), 12 nonsense (23.5%), 7 missense (13.7%), 5 duplication (9.8%) and 1 complex deletion/insertion (2.0%), 31 of which are novel mutations. The most common mutation is c.1735+1G>T (11.5%). The association of AGL missense and small in-frame deletion mutations with normal creatine kinase level was observed. Our study extends the spectrum of AGL mutations and suggests a genotype-phenotype correlation in GSD III.
authors.affiliation: McKusick-Zhang Center for Genetic Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medcine, Peking Union Medical College, Beijing, China.
authors.forename: Chaoxia
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zhengqing
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: McKusick-Zhang Center for Genetic Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medcine, Peking Union Medical College, Beijing, China.|Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.affiliation: McKusick-Zhang Center for Genetic Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medcine, Peking Union Medical College, Beijing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000483:Alleles; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002681:China; D019295:Computational Biology / Q000379:methods; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006004:Glycogen Debranching Enzyme System / Q000235:genetics*; D006010:Glycogen Storage Disease Type III / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype; D022821:RNA Splice Sites; D055815:Young Adult
chemical_list: D006004:Glycogen Debranching Enzyme System; D022821:RNA Splice Sites