TY - JOUR T1 - The severe form of type I hyperprolinaemia results from homozygous inactivation of the <em>PRODH</em> gene JF - Journal of Medical Genetics JO - J Med Genet SP - e7 LP - e7 DO - 10.1136/jmg.40.1.e7 VL - 40 IS - 1 AU - H Jacquet AU - J Berthelot AU - C Bonnemains AU - G Simard AU - P Saugier-Veber AU - G Raux AU - D Campion AU - D Bonneau AU - T Frebourg Y1 - 2003/01/01 UR - http://jmg.bmj.com/content/40/1/e7.abstract N2 - Since the original reports of hyperprolinaemia by Scriver et al1 and Shafer et al,2 two types of this rare metabolic disorder have been biochemically characterised3: type I (MIM 239500) results from the defect of the enzyme proline dehydrogenase (oxidase), which ensures the conversion of proline into Δ-1-pyrroline-5-carboxylate (P5C), the first step in the conversion from proline to glutamate,4 and type II (MIM 239510) is the result of a defect of the P5C dehydrogenase/aldehyde dehydrogenase 4 enzyme and P5C is excreted in the urine.5The phenotype of type II hyperprolinaemia is characterised by neurological manifestations including seizures and mental retardation.3,6,7 Although type I hyperprolinaemia was originally described in a kindred with a familial nephropathy,1,2 the renal disease was subsequently shown to be coincidental and type I hyperprolinaemia has been considered to be a benign disorder which can be asymptomatic.3 Nevertheless, two studies have reported severe neurological manifestations (mental retardation, epilepsy) in two male children with type I hyperprolinaemia.8,9 While mutations of the ALDH4A1 gene, located on chromosome 1p36, have been identified in families with type II hyperprolinaemia,10 the molecular basis of type I hyperprolinaemia has not been characterised until recently. We have recently identified in schizophrenic patients a heterozygous deletion and mutations of the PRODH gene, located on 22q11, which were associated with moderate hyperprolinaemia. We … ER -