Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

25-hydroxyvitamin D3 1-alpha-hydroxylase gene

The enzyme encoded by this gene activates vitamin D in the kidney. Calcidol resistant but Calcitriol remediable rickets result from inactivating mutation.

Epidemiology

A complete deficiency is extremly rare. there are about 30 families known world wide. Almost all of them carry there own mutation.

Gene Structure

The gene (CYP27B1) is about 5kb in size. Its position is on chromosome 12 (12q14) in proximity to vitamin D receptor. It consists of 9 exons. All of them are translated.

Phenotype

The newborn child with defective enzyme is normal but the symptoms of rickets develop early in childhood within the first two years. Growth retardation, muscular weakness and bone deformities are often. Low plasma levels of calcitriol (1,25-dihydroxy vitamin D3) are typical. And it can not be elevated by oral vitamin D3 substitution. Lifelong substitution of calcitriol is an effective therapy.

Pathology

The gene product an enzyme that catalyses hydroxylation of vitamin D3 is almost exclusively located in the kidney mitochondria. The translation is regulated by negative feedback mechanism of calcitriol - the end product of vitamin D activation. The enzyme by itself is the key enzyme in vitamin D activation.

Test Strategy

The necessity of genetic testing can be deduced from family counsultation and to provide prophylaxis to all family members without delay.

Interpretation

The importance of genetic testing is confirmation of the diagnosis in cases with difficult differential diagnosis. The result is necessary for genetic counsulting. A genotype phenotype correlation is not available yet.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 20 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Vitamin D hydroxylation-deficient rickets type 1A
CYP27B1

References:

1.

Kato S et al. (2002) Molecular genetics of vitamin D- dependent hereditary rickets.

[^]
Update: Sept. 26, 2018