title: A novel pathogenic mutation of the CYP27B1 gene in a patient with vitamin D-dependent rickets type 1: a case report.
abstract: BACKGROUND
  Rickets can occur due to Vitamin D deficiency or defects in its metabolism. Three rare genetic types of rickets with different alterations of genes have been reported, including: Vitamin D dependent rickets type 1, Vitamin D dependent rickets type 2 or also known as Vitamin D resistant rickets and 25 hydroxylase deficiency rickets. Vitamin D dependent rickets type 1 is inherited in an autosomal recessive pattern, and is caused by mutations in the CYP27B1 gene encoding the 1α-hydroxylase enzyme. We report here a new mutation in CYP27B1, which lead to Vitamin D dependent rickets type 1.
  
  
  METHODS
  We report on a 13-month-old Arabic Saudi girl with Vitamin D dependent rickets type 1 presented with multiple fractures and classic features of rickets. A whole exome sequencing identified a novel pathogenic missense mutation (CYP27B1:Homozygous c.1510C > T(p.Q504X)) which results in a protein truncating alteration. Both parents are heterozygous carriers of the mutation. Based on data search in Human Gene Mutation Database, 63 CYP27B1 alterations were reported: only 28.6% are protein truncating (5 nonsense, 13 frameshift insertions/deletions, 0 gross deletions), while 61.9% are non-truncating (38 missense, 1 small in-frame insertions/deletion), and 9.5% are possible protein-truncating (5 splice, 1 regulatory).
  
  
  CONCLUSIONS
  The deleterious effect of this alteration, which was the only mutation detected in the CYP27B1 common gene of Vitamin D dependent rickets type 1 in the proband, and its autosomal recessive inheritance fashion, both support a pathogenic nature of this mutation as the cause of Vitamin D dependent rickets type 1.
authors.affiliation: Pediatric Department, College of Medicine and King Khalid University Hospital, Riyadh, Saudi Arabia. babikeramir@hotmail.com.
authors.forename: Amir M I
authors.initials: AM
authors.lastname: Babiker
authors.forename: Iman
authors.initials: I
authors.lastname: Al Gadi
authors.forename: Nasir A M
authors.initials: NA
authors.lastname: Al-Jurayyan
authors.forename: Abdulrahman M H
authors.initials: AM
authors.lastname: Al Nemri
authors.forename: Ali Abdu N
authors.initials: AA
authors.lastname: Al Haboob
authors.forename: Ahmed Amer
authors.initials: AA
authors.lastname: Al Boukai
authors.forename: Ali
authors.initials: A
authors.lastname: Al Zahrani
authors.forename: Hanan Ahmed
authors.initials: HA
authors.lastname: Habib
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics*; D018912:Arabs / Q000235:genetics; D002118:Calcium / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D030541:Databases, Genetic; D019587:Dietary Supplements; D053098:Familial Hypophosphatemic Rickets / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006720:Homozygote; D006801:Humans; D007223:Infant; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D012529:Saudi Arabia; D014807:Vitamin D / Q000627:therapeutic use
chemical_list: D014807:Vitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002118:Calcium