title: Molecular analysis of Taiwanese patients with 3-hydroxy-3-methylglutaryl CoA lyase deficiency.
abstract: BACKGROUND
  3-Hydroxy-3-methylglutaryl CoA lyase deficiency (HL deficiency) is a rare autosomal recessive mitochondrial disease characterized by a deficiency in the enzyme 3-Hydroxy-3-methylglutaryl CoA lyase (HMGCL). Here, we report on novel mutations identified in the HMGCL gene in 2 Taiwanese patients with HL deficiency.
  
  
  METHODS
  Analysis of organic acids in urine was performed using gas chromatography-mass spectrometry to confirm HL deficiency in the two subjects. The mutations in their HMGCL genes then were determined by direct sequencing. In addition, the effect of a splice site mutation was determined using reverse transcription-polymerase chain reactions (RT-PCR).
  
  
  RESULTS
  A total of 3 novel mutations in the HMGCL gene were revealed by molecular analysis: one missense mutation (c.494G>T, p.Arg165Gln) and 2 splice site mutations (IVS3+1G>A, IVS6-1G>A). The results of RT-PCR revealed that an IVS3+1G>A mutation leads to skipping of exon3. We also calculated that the incidence of HL deficiency in Taiwan is <1 per 1,000,000 live births.
  
  
  CONCLUSIONS
  The results of this study suggest that unique HMGCL gene mutations exist in Taiwanese HL deficiency patients. Therefore, HMGCL gene profiling may be useful in genetic counseling for families affected by HL deficiency.
authors.affiliation: Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Wei-De
authors.initials: WD
authors.lastname: Lin
authors.forename: Chung-Hsing
authors.initials: CH
authors.lastname: Wang
authors.forename: Chien-Chen
authors.initials: CC
authors.lastname: Lai
authors.forename: Yushin
authors.initials: Y
authors.lastname: Tsai
authors.forename: Jer-Yuarn
authors.initials: JY
authors.lastname: Wu
authors.forename: Chih-Ping
authors.initials: CP
authors.lastname: Chen
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
mesh_terms: D000293:Adolescent; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D015994:Incidence; D008052:Lipid Metabolism, Inborn Errors / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D028361:Mitochondrial Diseases / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D009154:Mutation; D007652:Oxo-Acid-Lyases / Q000172:deficiency* / Q000235:genetics*; D013624:Taiwan / Q000453:epidemiology
chemical_list: D007652:Oxo-Acid-Lyases; C021410:3-hydroxy-3-methylglutaryl-coenzyme A lyase