ESPE Abstracts (2015) 84 P-2-220

Genotype and Phenotype Characteristics in 22 Patients with Vitamin D Dependent Rickets Type I

Sophia Tahira, Huseyin Demirbileka,b, Mehmet Nuri Ozbekc,d, Riza Taner Baranc, Sibel Tanriverdid & Khalid Hussaina,b


aGenetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme UCL Institute of Child Health, London, UK; bDepartment of Endocrinology, Great Ormond Street Hospital for Children, London, UK; cClinic of Paediatric Endocrinology, Diyarbakir Children State Hospital, Diyarbakir, Turkey; dDepartment of Padiatrics, Diyarbakir Training and Research Hospital, Diyarbakir, Turkey


Background: Vitamin D dependent rickets type I (VDDR1) is an autosomal recessive disorder caused by mutations in the 25-Hydroxyvitamin-D3 1-α-hydroxylase gene(CYP27B1).

Objective and hypotheses: To evaluate clinical characteristics and molecular genetic analysis of the pediatric patients with VDDR1 who were being followed at Diyarbakir Children’s State Hospital, Turkey.

Method: VDDR1 diagnosis was considered in course of clinical, biochemical and radiological characteristics of rickets with a normal or high 25(OH) vitamin-D level. Genomic DNA was extracted from peripheral blood leukocytes using a standard procedure. Mutation analysis was performed on all affected cases and subsequently on the unaffected family members where DNA was available. In silico analysis of the novel variants was performed using online available protein prediction software’s.

Results: In total 22 patients (11 females) from 13 families with VDDR1 recruited. The most common mutation which was detected in ten VDDR1 patients was a previously described, c.195+2T>G, splice donor site mutation. The novel missense p.192K>E(c.574A>G) mutation was detected in five patients, and a novel missense p.197G>D(c.590G>A) mutation was found in four patients. Previously reported 7 bp duplication mutation 1319–1325dupCCCACCC(Phe443Profs*24) in exon 8, was detected in one patient in the homozygous state. One patient was compound heterozygote for the novel p.192K>E and the previously described 1319–1325dupCCCACCC mutations. We also observed in one patient a novel single bp deletion, c.171_171delG, which causes a frame shift from protein 58 l and downstream, leading to an early stop. From the 36 unaffected family members, 28 were mono-allelic for the mutation detected in their family, and eight were biallelic for the normal reference allele.

Conclusion: In this study on the largest VDDR1 cohort, we identified three novel and two previously described mutations in the CYP27B1 gene. Mutation analysis, patient characteristics and sequencing results of unaffected family members revealed a good phenotype and genotype correlation.

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