title: Two siblings with a novel nonsense mutation, p.R50X, in the vitamin D receptor gene.
abstract: Hereditary vitamin D-resistant rickets (HVDRR), an autosomal recessive disorder caused by inactivating mutations in the vitamin D receptor (VDR) gene. We identified two affected children from the same family, one at the age of 10 years and 9 months and the other at 9 months old. Mutation analysis by PCR-sequencing the entire coding region of the VDR gene revealed a homozygous C to T transition in exon 2 of the VDR gene (c.148C>T) resulting in a stop codon at amino acid position 50 (p.R50X) in the proband and his younger sister. The p.R50X has never been previously described. Both asymptomatic parents were heterozygous for the mutation. In addition to most of the clinical features of HVDRR including total alopecia, symptoms of hypocalcemia at a later onset and normophosphatemia, rarely found in HVDRR were present in the proband. This study also emphasizes an important role of genetic testing for early diagnosis and genetic counseling.
authors.affiliation: Division of Endocrinology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Vichit
authors.initials: V
authors.lastname: Supornsilchai
authors.forename: Yodporn
authors.initials: Y
authors.lastname: Hiranras
authors.forename: Suttipong
authors.initials: S
authors.lastname: Wacharasindhu
authors.forename: Atchara
authors.initials: A
authors.lastname: Mahayosnond
authors.forename: Kanya
authors.initials: K
authors.lastname: Suphapeetiporn
authors.forename: Vorasuk
authors.initials: V
authors.lastname: Shotelersuk
mesh_terms: D000505:Alopecia / Q000175:diagnosis / Q000235:genetics; D002648:Child; D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis; D053098:Familial Hypophosphatemic Rickets / Q000175:diagnosis / Q000235:genetics*; D005817:Genetic Counseling; D005820:Genetic Testing; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D018167:Receptors, Calcitriol / Q000235:genetics*; D035781:Siblings
chemical_list: D018389:Codon, Nonsense; D018167:Receptors, Calcitriol