PMID- 10232633
OWN - NLM
STAT- MEDLINE
DCOM- 19990520
LR  - 20180330
IS  - 0002-9165 (Print)
IS  - 0002-9165 (Linking)
VI  - 69
IP  - 5
DP  - 1999 May
TI  - Biochemical but not clinical vitamin A deficiency results from mutations in the
      gene for retinol binding protein.
PG  - 931-6
AB  - BACKGROUND: Two German sisters aged 14 and 17 y were admitted to the Tubingen eye
      hospital with a history of night blindness. In both siblings, plasma retinol
      binding protein (RBP) concentrations were below the limit of detection (<0.6
      micromol/L) and plasma retinol concentrations were extremely low (0.19
      micromol/L). Interestingly, intestinal absorption of retinyl esters was normal.
      In addition, other factors associated with low retinol concentrations (eg, low
      plasma transthyretin or zinc concentrations or mutations in the transthyretin
      gene) were not present. Neither sibling had a history of systemic disease.
      OBJECTIVE: Our aim was to investigate the cause of the retinol deficiency in
      these 2 siblings. DESIGN: The 2 siblings and their mother were examined
      clinically, including administration of the relative-dose-response test, DNA
      sequencing of the RBP gene, and routine laboratory testing. RESULTS: Genomic DNA 
      sequence analysis revealed 2 point mutations in the RBP gene: a T-to-A
      substitution at nucleotide 1282 of exon 3 and a G-to-A substitution at nucleotide
      1549 of exon 4. These mutations resulted in amino acid substitutions of
      asparagine for isoleucine at position 41 (Ile41-->Asn) and of aspartate for
      glycine at position 74 (Gly74-->Asp). Sequence analysis of cloned polymerase
      chain reaction products spanning exons 3 and 4 showed that these mutations were
      localized on different alleles. The genetic defect induced severe biochemical
      vitamin A deficiency but only mild clinical symptoms (night blindness and a
      modest retinal dystrophy without effects on growth). CONCLUSIONS: We conclude
      that the cellular supply of vitamin A to target tissues might be bypassed in
      these siblings via circulating retinyl esters, beta-carotene, or retinoic acid,
      thereby maintaining the health of peripheral tissues.
FAU - Biesalski, H K
AU  - Biesalski HK
AD  - Department of Biological Chemistry and Nutrition, University Hohenheim,
      Stuttgart, Germany. biesal@uni-hohenheim.de
FAU - Frank, J
AU  - Frank J
FAU - Beck, S C
AU  - Beck SC
FAU - Heinrich, F
AU  - Heinrich F
FAU - Illek, B
AU  - Illek B
FAU - Reifen, R
AU  - Reifen R
FAU - Gollnick, H
AU  - Gollnick H
FAU - Seeliger, M W
AU  - Seeliger MW
FAU - Wissinger, B
AU  - Wissinger B
FAU - Zrenner, E
AU  - Zrenner E
LA  - eng
SI  - GENBANK/AF025334
SI  - GENBANK/AF025335
PT  - Journal Article
PL  - United States
TA  - Am J Clin Nutr
JT  - The American journal of clinical nutrition
JID - 0376027
RN  - 0 (Prealbumin)
RN  - 0 (Retinol-Binding Proteins)
RN  - 0 (Retinol-Binding Proteins, Plasma)
RN  - 11103-57-4 (Vitamin A)
RN  - 1D1K0N0VVC (retinol palmitate)
RN  - J41CSQ7QDS (Zinc)
SB  - AIM
SB  - IM
CIN - Am J Clin Nutr. 1999 May;69(5):829-30. PMID: 10232619
EIN - Am J Clin Nutr 2000 Apr;71(4):1010
MH  - Adolescent
MH  - Base Sequence
MH  - Exons
MH  - Female
MH  - Humans
MH  - Molecular Sequence Data
MH  - Nuclear Family
MH  - Point Mutation
MH  - Prealbumin/chemistry/genetics
MH  - Retinol-Binding Proteins/*genetics/metabolism
MH  - Retinol-Binding Proteins, Plasma
MH  - Vitamin A/analogs & derivatives/blood/pharmacology
MH  - Vitamin A Deficiency/blood/*genetics/metabolism
MH  - Zinc/blood
EDAT- 1999/05/08 02:12
MHDA- 2000/05/29 09:00
CRDT- 1999/05/08 02:12
PHST- 1999/05/08 02:12 [pubmed]
PHST- 2000/05/29 09:00 [medline]
PHST- 1999/05/08 02:12 [entrez]
AID - 10.1093/ajcn/69.5.931 [doi]
PST - ppublish
SO  - Am J Clin Nutr. 1999 May;69(5):931-6. doi: 10.1093/ajcn/69.5.931.