ISSN: 1308-5727 | E-ISSN: 1308-5735
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Turkish Society for Pediatric Endocrinology and Diabetes
Genetic and Clinical Characteristics of Patients with Vitamin D Dependent Rickets Type 1A [J Clin Res Pediatr Endocrinol]
J Clin Res Pediatr Endocrinol. 2019; 11(1): 34-40 | DOI: 10.4274/jcrpe.galenos.2018.2018.0121

Genetic and Clinical Characteristics of Patients with Vitamin D Dependent Rickets Type 1A

Fatma Dursun1, Gamze Özgürhan2, Heves Kırmızıbekmez1, Ece Keskin3, Bülent Hacıhamdioğlu4
1Ümraniye Training and Research Hospital, Clinic of Pediatric Endocrinology, İstanbul, Turkey
2Süleymaniye Maternity and Children’s Training and Research Hospital, Clinic of Paediatrics, İstanbul, Turkey
3Süleymaniye Maternity and Children’s Training and Research Hospital, Clinic of Medical Genetic, İstanbul, Turkey
4İstinye University Faculty of Medicine, Department of Pediatric Endocrinology, İstanbul, Turkey

Objective: Vitamin D dependent rickets type 1A (VDDR1A) is an autosomal recessive disorder caused by mutations in the 1?-hydroxylase gene (CYB27B1). As it may be confused with nutritional rickets and hypophosphatemic rickets, genetic analysis is important for making a correct diagnosis.
Methods: We analysed genomic DNA from 11 patients from eight different Turkish families. The patients were recruited for our studies if they presented with a diagnosis of VDDR.
Results: The mean ± standard deviation age at diagnosis was 13.1±7.4 months. Seven patients had mild hypocalcemia at presentation while four patients had normal calcium concentrations. All patients underwent CYP27B1 gene analysis. The most prevalent mutation was the c.195 + 2T>G splice donor site mutation, affecting five out of 11 patients with VDDR1A. Two patients from the fourth family were compound heterozygous for c.195 + 2T>G and c.195 + 2 T>A in intron-1. Two patients, from different families, were homozygous for a previously reported duplication mutation in exon 8 (1319_1325dupCCCACCC, Phe443Profs*24). One patient had a homozygous splice site mutation in intron 7 (c.1215 + 2 T>A) and one patient had a homozygous mutation in exon 9 (c.1474 C>T).
Conclusion: Intron-1 mutation was the most common mutation, as previously reported. All patients carrying that mutation were from same city of origin suggesting a “founder” or a “common ancestor” effect. VDDR1A should definitely be considered when a patient with signs of rickets has a normal 25-OHD level or when there is unresponsiveness to vitamin D treatment.

Keywords: Vitamin D, vitamin D dependent rickets, CYP27B1 gene, 1? hydroxylase

Fatma Dursun, Gamze Özgürhan, Heves Kırmızıbekmez, Ece Keskin, Bülent Hacıhamdioğlu. Genetic and Clinical Characteristics of Patients with Vitamin D Dependent Rickets Type 1A. J Clin Res Pediatr Endocrinol. 2019; 11(1): 34-40
Manuscript Language: English
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