A Novel Missense Mutation (C84R) in a Patient with Type II Vitamin D-dependent Rickets

Abstract

A 7-year-old boy with severe rickets that by clinical analysis was diagnosed as affected by type II vitamin D-dependent rickets, was evaluated for mutations in the vitamin D receptor gene (VDR). The molecular analysis showed a homozygous state for a novel missense mutation (C84R) in a highly conserved nucleotide in the second Zn finger of the DNA binding domain.

Key words

vitamin D dependent rickets type II - vitamin D receptor - missense mutant

References

• 1 Hughes MR, Malloy PJ, Kieback DG. et al . Point mutations in the human vitamin D receptor gene associated with hypocalcemic rickets.  Science. 1988;  242 1702-1705
• 2 Kristjansson K, Rut AR, Hewison M. et al . Two mutations in the hormone binding domain of the vitamin D receptor cause tissue resistance to 1,25 dihydroxyvitamin D3.  J Clin Invest. 1993;  92 12-16
• 3 Lin NU, Malloy PJ, Sakati N. et al . A novel mutation in the deoxyribonucleic acid-binding domain of the vitamin D receptor causes hereditary 1,25-dihydroxyvitamin D-resistant rickets.  J Clin Endocrinol Metab. 1996;  81 2564-2569
• 4 Malloy PJ, Eccleshall TR, Gross C. et al . Hereditary vitamin D resistant rickets caused by a novel mutation in the vitamin D receptor that results in decreased affinity for hormone and cellular hyporesponsiveness.  J Clin Invest. 1997;  99 297-304
• 5 Mechica JB, Leite MO, Mendonca BB. et al . A novel nonsense mutation in the first zinc finger of the vitamin D receptor causing hereditary 1,25-dihydroxyvitamin D3-resistant rickets.  J Clin Endocrinol Metab. 1997;  82 3892-3894
• 6 Miyamoto K, Kesterson RA, Yamamoto H. et al . Structural organization of the human vitamin D receptor chromosomal gene and its promoter.  Mol Endocrinol. 1997;  11 1165-1179
• 7 Ritchie HH, Hughes MR, Thompson ET. et al . An ochre mutation in the vitamin D receptor gene causes hereditary 1,25-dihydroxyvitamin D3-resistant rickets in three families.  Proc Natl Acad Sci USA. 1989;  86 9783-9787
• 8 Saijo T, Ito M, Takeda E. et al . A unique mutation in the vitamin D receptor gene in three Japanese patients with vitamin D-dependent rickets type II: utility of single-strand conformation polymorphism analysis for heterozygous carrier detection.  Am J Hum Genet. 1991;  49 668-673
• 9 Sone T, Scott RA, Hughes MR. et al . Mutant vitamin D receptors which confer hereditary resistance to 1,25-dihydroxyvitamin D3 in humans are transcriptionally inactive in vitro.  J Biol Chem. 1989;  264 20230-20234
• 10 Takeda E, Yokota I, Kawakami I. et al . Two siblings with vitamin-D-dependent rickets type II: no recurrence of rickets for 14 years after cessation of therapy.  Eur J Pediatr. 1989;  149 54-57
• 11 Maldergem L Van, Bachy A, Feldman D. et al . Syndrome of lipoatrophic diabetes, vitamin D resistant rickets, and persistent Mullerian ducts in a Turkish boy born to consanguineous parents.  Am J Med Genet. 1996;  64 506-513
• 12 Whitfield GK, Selznick SH, Haussler CA. et al . Vitamin D receptors from patients with resistance to 1,25-dihydroxyvitamin D3: point mutations confer reduced transactivation in response to ligand and impaired interaction with the retinoid X receptor heterodimeric partner.  Mol Endocrinol. 1996;  10 1617-1631

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