title: Different gene preferences of maple syrup urine disease in the aboriginal tribes of Taiwan.
abstract: BACKGROUND
  Maple syrup urine disease (MSUD) is a rare inborn error of metabolism caused by a deficiency of the branched-chain α-ketoacid dehydrogenase (BCKD) complex. Mutations in any one of the three different genes encoding for the BCKD components, namely, BCKDHA, BCKDHB, and DBT, may be responsible for this disease. In Taiwan, few MSUD cases were diagnosed clinically, and most of these patients are from Aboriginal tribes.
  
  
  METHODS
  To identify and detect the carrier frequency of MSUD in Taiwanese Aboriginal tribes, we performed biochemical and molecular studies from peripheral blood in MSUD patients and dried blood on filter paper in the enrolled screened populations.
  
  
  RESULTS
  Homozygous A208T and I281T of BCKDHA were found in two patients from Hans (non-Aboriginal Taiwanese), respectively; compound heterozygous mutations of the DBT gene [4.7 kb deletion/c.650-651insT (L217F or L217fsX223) and c.650-651insT/c.88-89delAT] were found in two patients from Amis, respectively, after direct DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism studies. There were no cases of deleted 4.7-kb heterozygote out of 302 normal people (Hans, n = 125; Atayal, n = 156; and Saisiyat, n = 21); by contrast, the DBT mutations c.650-651insT and deleted 4.7-kb heterozygote were noted in 2/121 and 1/121, respectively, from the general population of the Amis, a southeastern Taiwanese tribe.
  
  
  CONCLUSIONS
  Although the Taiwanese Austronesian Aboriginal tribes are considered to share a common origin, different gene preferences of MSUD were noted. The novel DBT mutation c.650-651insT was more prevalent than the deleted 4.7-kb heterozygote in the Amis population. The reported 4.7-kb deletion indicating a possible founder mutation may be preserved in the southern and eastern, but not in northern Aboriginal tribes of Taiwan.
authors.affiliation: Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan; Department of Pediatrics, Fu-Jen Catholic University School of Medicine, New Taipei City, Taiwan. Electronic address: hou76@cgh.org.tw.
authors.forename: Jia-Woei
authors.initials: JW
authors.lastname: Hou
authors.affiliation: Department of Surgery, Chang Gung University School of Medicine, Taoyuan, Taiwan.
authors.forename: Tsann-Long
authors.initials: TL
authors.lastname: Hwang
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000235:genetics*; D000217:Acyltransferases / Q000235:genetics*; D000328:Adult; D000368:Aged; D044466:Asian People / Q000208:ethnology; D005260:Female; D018703:Founder Effect; D006579:Heterozygote; D006801:Humans; D008297:Male; D008375:Maple Syrup Urine Disease / Q000208:ethnology* / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
chemical_list: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000217:Acyltransferases; C033588:dihydrolipoamide acyltransferase
keywords: Taiwanese Aboriginal Austronesian tribe; carrier frequency; dihydrolipoyl transacetylase gene; gene preference; maple syrup urine disease