title: Identification of PRODH mutations in Korean neonates with type I hyperprolinemia.
abstract: BACKGROUND
  Hyperprolinemia is a rare inherited metabolic disorder characterized by a high proline level in blood and/or urine and various neuropsychiatric symptoms. Type I hyperprolinemia is caused by a proline oxidase deficiency, which is encoded by the PRODH gene on chromosome 22q11. Herein, we present a study of Korean patients with type I hyperprolinemia who were diagnosed during newborn screening by tandem mass spectrometry and confirmed by molecular analysis.
  
  
  METHODS
  Four neonates were referred to our hospital for workup of high proline levels in newborn screening test. We analyzed the biochemical findings and the PRODH gene was amplified by long-range PCR to confirm molecular genetic abnormalities.
  
  
  RESULTS
  All patients had high plasma proline levels, ranging from 742 to 1192 μmol/L (reference range, 77.4 - 244.6 μmol/L). In molecular analysis, 4 disease-associated mutant alleles were identified: c.1414G>A (p.A472T), c.1279G>A (p.V427M), c.1357C>T (p.R453C) and c.1562A>G (p.Q521R). All mutations were missense and c.1279G>A included the majority of mutant alleles. No relationships between type of mutation and clinical outcomes were observed.
  
  
  CONCLUSIONS
  We found that distinct molecular alterations of the PRODH gene result in abnormal proline levels. Newborn screening and molecular analysis are necessary to identify patients before clinical expression of metabolic disease.
authors: Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Mi-Ae
authors: MA
authors: Jang
authors: Byung Cheol
authors: BC
authors: Kim
authors: Chang-Seok
authors: CS
authors: Ki
authors: Soo-Youn
authors: SY
authors: Lee
authors: Jong-Won
authors: JW
authors: Kim
authors: Tae Youn
authors: TY
authors: Choi
authors: Dong Hwan
authors: DH
authors: Lee
authors: Junghan
authors: J
authors: Song
authors: Yong-Wha
authors: YW
authors: Lee
authors: Hyung-Doo
authors: HD
authors: Park
mesh_terms: D050842:1-Pyrroline-5-Carboxylate Dehydrogenase / Q000172:deficiency; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics; D011394:Proline Oxidase / Q000172:deficiency / Q000235:genetics*; D056910:Republic of Korea
chemical_list: D050842:1-Pyrroline-5-Carboxylate Dehydrogenase; D011394:Proline Oxidase; C582834:PRODH protein, human