PMID- 9360557
OWN - NLM
STAT- MEDLINE
DCOM- 19971125
LR  - 20220408
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 82
IP  - 11
DP  - 1997 Nov
TI  - A novel nonsense mutation in the first zinc finger of the vitamin D receptor 
      causing hereditary 1,25-dihydroxyvitamin D3-resistant rickets.
PG  - 3892-4
AB  - Hereditary 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-resistant rickets (HVDRR) is a 
      rare autosomal recessive disorder resulting in target organ resistance to the 
      active form of vitamin D [1,25-(OH)2D3]. Point mutations in the vitamin D 
      receptor (VDR) gene have been identified in HVDRR. We investigated the molecular 
      basis of HVDRR in a Brazilian family with two affected siblings. The propositus 
      is a 12-yr-old boy born to first cousin parents who exhibited the classical 
      pattern of the HVDRR, including early-onset rickets, total alopecia, convulsions, 
      hypocalcemia, secondary hyperparathyroidism, and elevated 1,25-(OH)2D3 serum 
      levels. His younger sister also developed clinical and biochemical features of 
      HVDRR at 1 month of age and died at 4 yr of age. Genomic DNA was isolated from 
      peripheral blood of the boy and from dried umbilical cord tissue of his affected 
      sister. We amplified exons 2 and 3 of the VDR gene, which encode the zinc finger 
      DNA-binding domain by PCR. Direct sequencing of the PCR products revealed a 
      homozygous substitution of cytosine for thymine at nucleotide position 88 in exon 
      2 of the VDR gene in both affected siblings. This point mutation determined the 
      substitution of a stop codon (TGA) for arginine (CGA) at amino acid position 30 
      at the first zinc finger of the DNA-binding domain of the VDR. This substitution 
      generated a truncated receptor missing 397 residues. The parents and a normal 
      sister were heterozygous for this mutation. In conclusion, we describe a novel 
      nonsense mutation in the first zinc finger of the VDR that generated a severely 
      truncated form of this receptor.
FAU - Mechica, J B
AU  - Mechica JB
AD  - Division of Endocrinology, Hospital das Clinicas, University of Sao Paulo, 
      Brazil.
FAU - Leite, M O
AU  - Leite MO
FAU - Mendonca, B B
AU  - Mendonca BB
FAU - Frazzatto, E S
AU  - Frazzatto ES
FAU - Borelli, A
AU  - Borelli A
FAU - Latronico, A C
AU  - Latronico AC
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Codon)
RN  - 0 (DNA, Complementary)
RN  - 0 (Receptors, Calcitriol)
RN  - 94ZLA3W45F (Arginine)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - Arginine/genetics
MH  - Base Sequence
MH  - Calcitriol/blood
MH  - Child
MH  - Codon
MH  - DNA, Complementary/chemistry
MH  - Humans
MH  - Hypophosphatemia, Familial/diagnosis/*genetics
MH  - Male
MH  - Pedigree
MH  - *Point Mutation
MH  - Polymerase Chain Reaction
MH  - Receptors, Calcitriol/*genetics
MH  - *Zinc Fingers
EDAT- 1997/11/14 00:00
MHDA- 1997/11/14 00:01
CRDT- 1997/11/14 00:00
PHST- 1997/11/14 00:00 [pubmed]
PHST- 1997/11/14 00:01 [medline]
PHST- 1997/11/14 00:00 [entrez]
AID - 10.1210/jcem.82.11.4384 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1997 Nov;82(11):3892-4. doi: 10.1210/jcem.82.11.4384.