The enzyme encoded by this gene activates vitamin D in the kidney. Calcidol resistant but Calcitriol remediable rickets result from inactivating mutation.
A complete deficiency is extremly rare. there are about 30 families known world wide. Almost all of them carry there own mutation.
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.
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.
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.
The necessity of genetic testing can be deduced from family counsultation and to provide prophylaxis to all family members without delay.
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.
Clinic | Method | Carrier testing |
Turnaround | 5 days | |
Specimen type | genomic DNA |
Clinic | Method | Massive parallel sequencing |
Turnaround | 25 days | |
Specimen type | genomic DNA |
Clinic | Method | Genomic sequencing of the entire coding region |
Turnaround | 20 days | |
Specimen type | genomic DNA |
1. |
Kato S et al. (2002) Molecular genetics of vitamin D- dependent hereditary rickets. |
2. |
Orphanet article Orphanet ID 120994 |
3. |
NCBI article NCBI 1594 |
4. |
OMIM.ORG article Omim 609506 |
5. |
Wikipedia article Wikipedia EN (25-Hydroxyvitamin_D3_1-alpha-hydroxylase) |