title: Mutation analysis and prenatal diagnosis in a Chinese family with succinic semialdehyde dehydrogenase and a systematic review of the literature of reported ALDH5A1 mutations.
abstract: OBJECTIVE
  Succinic semialdehyde dehydrogenase (SSADH) deficiency is a neurometabolic disease in which the degradation of γ-aminobutyric acid (GABA) is impaired. The purpose of this study was to report two novel ALDH5A1 mutations responsible for SSADH deficiency in a Chinese family and the prenatal diagnosis of an at-risk fetus with DNA sequencing.
  
  
  RESULTS
  Genetic analysis of ALDH5A1, in a child with SSADH deficiency, parents, and 10 weeks' gestation at-risk fetus and 100 healthy unrelated volunteers, was performed. The coding sequence and the intron/exon junctions of ALDH5A1 were analyzed by bidirectional DNA sequencing. The proband was identified to have a compound heterozygous mutations with c.496T>C (p.W166R) and c.589G>A (p.V197M). Each of his parents carried a deleterious mutation. DNA sequencing of chorionic villus revealed the fetus was a carrier, but not affected, and this was confirmed after birth by genetic analysis of umbilical cord blood and urine organic acid analysis. A study in 2003 described 35 mutations of ALDH5A1 in 54 unrelated families, and the current study and systematic literature review identified nine additional novel mutations in eight unrelated families bringing the total number of unique mutations of ALDH5A1 resulting in SSADH deficiency to 44, and the 44 mutations occur from exon 1 to exon 10. No mutational hotspots or prevalent mutations were observed, and all mutations appeared vital for the function of SSADH.
  
  
  CONCLUSIONS
  Two novel ALDH5A1 mutations likely responsible for SSADH deficiency were identified, and DNA sequencing provided an accurate diagnosis for an at-risk fetus whose sibling had SSADH deficiency.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Kong
authors.forename: Quan-Cheng
authors.initials: QC
authors.lastname: Kan
authors.forename: Hui-Rong
authors.initials: HR
authors.lastname: Shi
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Wu
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Zhuo
authors.forename: Qiao-Ling
authors.initials: QL
authors.lastname: Bai
authors.forename: Miao
authors.initials: M
authors.lastname: Jiang
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D011247:Pregnancy; D011296:Prenatal Diagnosis; D050644:Succinate-Semialdehyde Dehydrogenase / Q000172:deficiency* / Q000235:genetics
chemical_list: C493643:ALDH5A1 protein, human; D050644:Succinate-Semialdehyde Dehydrogenase