title: Detection of Hereditary 1,25-Hydroxyvitamin D-Resistant Rickets Caused by Uniparental Disomy of Chromosome 12 Using Genome-Wide Single Nucleotide Polymorphism Array.
abstract: BACKGROUND
  Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is an autosomal recessive disease caused by biallelic mutations in the vitamin D receptor (VDR) gene. No patients have been reported with uniparental disomy (UPD).
  
  
  OBJECTIVE
  Using genome-wide single nucleotide polymorphism (SNP) array to confirm whether HVDRR was caused by UPD of chromosome 12.
  
  
  METHODS
  A 2-year-old girl with alopecia and short stature and without any family history of consanguinity was diagnosed with HVDRR by typical laboratory data findings and clinical features of rickets. Sequence analysis of VDR was performed, and the origin of the homozygous mutation was investigated by target SNP sequencing, short tandem repeat analysis, and genome-wide SNP array.
  
  
  RESULTS
  The patient had a homozygous p.Arg73Ter nonsense mutation. Her mother was heterozygous for the mutation, but her father was negative. We excluded gross deletion of the father's allele or paternal discordance. Genome-wide SNP array of the family (the patient and her parents) showed complete maternal isodisomy of chromosome 12. She was successfully treated with high-dose oral calcium.
  
  
  CONCLUSIONS
  This is the first report of HVDRR caused by UPD, and the third case of complete UPD of chromosome 12, in the published literature. Genome-wide SNP array was useful for detecting isodisomy and the parental origin of the allele. Comprehensive examination of the homozygous state is essential for accurate genetic counseling of recurrence risk and appropriate monitoring for other chromosome 12 related disorders. Furthermore, oral calcium therapy was effective as an initial treatment for rickets in this instance.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Tamura
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Isojima
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Minae
authors.initials: M
authors.lastname: Kawashima
authors.affiliation: Department of Pediatrics, North Medical Center, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Kitaoka
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Namba
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Oka
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ozono
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kitanaka
mesh_terms: D000284:Administration, Oral; D000483:Alleles; D000505:Alopecia / Q000235:genetics; D001827:Body Height; D002118:Calcium / Q000008:administration & dosage; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12; D019587:Dietary Supplements; D005260:Female; D015894:Genome, Human; D006130:Growth Disorders / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006887:Hydroxycholecalciferols / Q000008:administration & dosage; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D063730:Rickets, Hypophosphatemic / Q000175:diagnosis* / Q000235:genetics*; D024182:Uniparental Disomy / Q000235:genetics*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D006887:Hydroxycholecalciferols; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D002118:Calcium; C008088:alfacalcidol