title: Novel Vitamin D Receptor Mutations in Hereditary Vitamin D Resistant Rickets in Chinese.
abstract: Hereditary 1, 25-dihydroxyvitamin D-resistant rickets (HVDRR), a rare recessive disease, is caused by mutation in the VDR gene encoding the vitamin D receptor leading to the resistance to vitamin D. We described a female toddler with initial presentation of leg tenderness and clinical features of HVDRR including severe rickets, hypocalcemia and hypophosphatemia without alopecia. Genetic analysis revealed novel compound heterozygous mutations of p.M4I and p.H229Q in patient's VDR gene. In cis p.M4I with FOKI-F eliminated both translation start sites of the VDR protein. The p.H229Q VDR exhibited significantly reduced VDR transactivation activity with intact dimerization with RXR. Our report expanded the mutation spectrum of HVDRR, and provided the first case of a benign variant p.M4I plus a common p.M1T polymorphism leading to a pathogenic allele.
authors.affiliation: Division of Nephrology, Department of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Lee-Moay
authors.initials: LM
authors.lastname: Lim
authors.affiliation: Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH, United States of America.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Division of Genetics, Endocrinology and Metabolism, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Mei-Chyn
authors.initials: MC
authors.lastname: Chao
authors.affiliation: Department of Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan; Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Jer-Ming
authors.initials: JM
authors.lastname: Chang
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy Taipei Medical University, Taipei, Taiwan; Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chang
authors.affiliation: Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH, United States of America.
authors.forename: Hung-Ying
authors.initials: HY
authors.lastname: Kao
authors.affiliation: Division of Nephrology, Department of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Center for Lipid and Glycomedicine Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Daw-Yang
authors.initials: DY
authors.lastname: Hwang
authors.affiliation: Division of Nephrology, Department of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hung-Chun
authors.initials: HC
authors.lastname: Chen
mesh_terms: D000483:Alleles; D000818:Animals; D044466:Asian People; D019556:COS Cells; D002681:China; D002522:Chlorocebus aethiops; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D057809:HEK293 Cells; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D018167:Receptors, Calcitriol / Q000235:genetics*; D012279:Rickets / Q000235:genetics*; D014807:Vitamin D / Q000494:pharmacology
chemical_list: D018167:Receptors, Calcitriol; D014807:Vitamin D