PMID- 10566658
OWN - NLM
STAT- MEDLINE
DCOM- 19991126
LR  - 20191210
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 84
IP  - 11
DP  - 1999 Nov
TI  - No enzyme activity of 25-hydroxyvitamin D3 1alpha-hydroxylase gene product in
      pseudovitamin D deficiency rickets, including that with mild clinical
      manifestation.
PG  - 4111-7
AB  - Pseudovitamin D deficiency rickets (PDDR) is an autosomal recessive disorder
      caused by defect in the activation of vitamin D. We recently isolated
      25-hydroxyvitamin D3 1alpha-hydroxylase gene and identified four homozygous
      inactivating missense mutations in this gene by analysis of four typical cases of
      PDDR. This disease shows some phenotypic variation, and it has been suspected
      that patients with mild phenotypes have mutations that do not totally abolish the
      enzyme activity. To investigate the molecular defects associated with the
      phenotypic variation, we analyzed six additional unrelated PDDR patients: one
      with mild and five with typical clinical manifestation. By sequence analysis, all
      six patients were proven to have mutations in both alleles. The mutations varied,
      and we identified four novel missense mutations, a nonsense mutation, and a
      splicing mutation for the first time. The patient with mild clinical symptoms was
      compound heterozygous for T321R and a splicing mutation. The splice site mutation
      caused intron retention. Enzyme activity of the T321R mutant was analyzed by
      overexpressing the mutant 1alpha-hydroxylase in Escherichia coli cells to detect 
      the subtle residual enzyme activity. No residual enzyme activity was detected in 
      T321R mutant or in the other mutants. These results indicate that all of the
      patients, including those of mild phenotype, are caused by 1alpha-hydroxylase
      gene mutations that totally abolish the enzyme activity.
FAU - Kitanaka, S
AU  - Kitanaka S
AD  - Institute of Molecular and Cellular Biosciences, The University of Tokyo, Japan.
FAU - Murayama, A
AU  - Murayama A
FAU - Sakaki, T
AU  - Sakaki T
FAU - Inouye, K
AU  - Inouye K
FAU - Seino, Y
AU  - Seino Y
FAU - Fukumoto, S
AU  - Fukumoto S
FAU - Shima, M
AU  - Shima M
FAU - Yukizane, S
AU  - Yukizane S
FAU - Takayanagi, M
AU  - Takayanagi M
FAU - Niimi, H
AU  - Niimi H
FAU - Takeyama, K
AU  - Takeyama K
FAU - Kato, S
AU  - Kato S
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - EC 1.14.15.18 (25-Hydroxyvitamin D3 1-alpha-Hydroxylase)
SB  - IM
MH  - 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics/*metabolism
MH  - Alleles
MH  - DNA Mutational Analysis
MH  - Female
MH  - Humans
MH  - Infant
MH  - Male
MH  - *Mutation
MH  - Mutation, Missense
MH  - Pedigree
MH  - Phenotype
MH  - RNA Splicing
MH  - Rickets/enzymology/*genetics
MH  - Vitamin D Deficiency/*genetics
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - 10.1210/jcem.84.11.6131 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1999 Nov;84(11):4111-7. doi: 10.1210/jcem.84.11.6131.