PMID- 21487760
OWN - NLM
STAT- MEDLINE
DCOM- 20111024
LR  - 20231213
IS  - 1573-2665 (Electronic)
IS  - 0141-8955 (Linking)
VI  - 34
IP  - 3
DP  - 2011 Jun
TI  - Defect in proline synthesis: pyrroline-5-carboxylate reductase 1 deficiency leads 
      to a complex clinical phenotype with collagen and elastin abnormalities.
PG  - 731-9
LID - 10.1007/s10545-011-9319-3 [doi]
AB  - Pyrroline-5-carboxylate reductase 1 (PYCR1) catalyzes the last step in proline 
      synthesis. Deficiency of PYCR1, caused by a defect in PYCR1, was recently 
      described in patients with cutis laxa, intrauterine growth retardation, 
      developmental dysplasia of the hips and mental retardation. In this paper, we 
      describe additional six patients (ages ranging from 4 months to 55 years) from 
      four Iranian families with clinical manifestations of a wrinkly skin disorder. 
      All patients have distinct facial features comprising triangular face, loss of 
      adipose tissue and thin pointed nose. Additional features are short stature, 
      wrinkling over dorsum of hand and feet, visible veins over the chest and 
      hyperextensible joints. Three of the patients from a large consanguineous family 
      do not have mental retardation, while the remaining three patients from three 
      unrelated families have mental and developmental delay. Mutation analysis 
      revealed the presence of disease-causing variants in PYCR1, including a novel 
      deletion of the entire PYCR1 gene in one family, and in each of the other 
      patients the homozygous missense mutations c.616G > A (p.Gly206Arg), c.89T > A 
      (p.Ile30Lys) and c.572G > A (p.Gly191Glu) respectively, the latter two of which 
      are novel. Light- and electron microscopy investigations of skin biopsies showed 
      smaller and fragmented elastic fibres, abnormal morphology of the mitochondria 
      and their cristae, and slightly abnormal collagen fibril diameters with irregular 
      outline and variable size. In conclusion, this study adds information on the 
      natural course of PYCR1 deficiency and sheds light on the pathophysiology of this 
      disorder. However, the exact pathogenesis of this new disorder and the role of 
      proline in the development of the clinical phenotype remain to be fully 
      explained.
FAU - Kretz, Rita
AU  - Kretz R
AD  - Division of Metabolism, Kinderspital Zurich, Pediatric Research Centre, 
      Steinwiesstrasse 75, 8032 Zurich, Switzerland.
FAU - Bozorgmehr, Bita
AU  - Bozorgmehr B
FAU - Kariminejad, Mohamad Hasan
AU  - Kariminejad MH
FAU - Rohrbach, Marianne
AU  - Rohrbach M
FAU - Hausser, Ingrid
AU  - Hausser I
FAU - Baumer, Alessandra
AU  - Baumer A
FAU - Baumgartner, Matthias
AU  - Baumgartner M
FAU - Giunta, Cecilia
AU  - Giunta C
FAU - Kariminejad, Ariana
AU  - Kariminejad A
FAU - Haberle, Johannes
AU  - Haberle J
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20110413
PL  - United States
TA  - J Inherit Metab Dis
JT  - Journal of inherited metabolic disease
JID - 7910918
RN  - 0 (Pyrroles)
RN  - 2906-39-0 (delta-1-pyrroline-5-carboxylate)
RN  - 9007-34-5 (Collagen)
RN  - 9007-58-3 (Elastin)
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 1.5.1.- (Pyrroline Carboxylate Reductases)
SB  - IM
MH  - Abnormalities, Multiple/*genetics/metabolism
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Child, Preschool
MH  - Collagen/*deficiency/metabolism
MH  - DNA Mutational Analysis
MH  - Elastin/*deficiency/metabolism
MH  - Family
MH  - Female
MH  - Humans
MH  - Infant
MH  - Male
MH  - Metabolism, Inborn Errors/complications/*genetics
MH  - Middle Aged
MH  - Models, Biological
MH  - Mutation, Missense
MH  - Phenotype
MH  - Proline/biosynthesis/*deficiency
MH  - Pyrroles/metabolism
MH  - Pyrroline Carboxylate Reductases/deficiency/*genetics
MH  - Young Adult
MH  - delta-1-Pyrroline-5-Carboxylate Reductase
EDAT- 2011/04/14 06:00
MHDA- 2011/10/25 06:00
CRDT- 2011/04/14 06:00
PHST- 2011/01/26 00:00 [received]
PHST- 2011/03/18 00:00 [accepted]
PHST- 2011/03/15 00:00 [revised]
PHST- 2011/04/14 06:00 [entrez]
PHST- 2011/04/14 06:00 [pubmed]
PHST- 2011/10/25 06:00 [medline]
AID - 10.1007/s10545-011-9319-3 [doi]
PST - ppublish
SO  - J Inherit Metab Dis. 2011 Jun;34(3):731-9. doi: 10.1007/s10545-011-9319-3. Epub 
      2011 Apr 13.