A novel pathogenic mutation of the CYP27B1 gene in a patient with vitamin D-dependent rickets type 1: a case report
| Autor: | Nasir A.M. Al-Jurayyan, Ali Abdu N Al Haboob, Ahmed Amer Al Boukai, Hanan A. Habib, Iman Al Gadi, Ali Al Zahrani, Amir Babiker, Abdulrahman Al Nemri |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
medicine.medical_specialty
Heredity DNA Mutational Analysis Mutation Missense Saudi Arabia Rickets Case Report Gene mutation medicine.disease_cause General Biochemistry Genetics and Molecular Biology vitamin D deficiency Frameshift mutation CYP27B1 Internal medicine Databases Genetic medicine Vitamin D and neurology Missense mutation Humans Genetic Predisposition to Disease Vitamin D VDDR-1 Genetics 25-Hydroxyvitamin D3 1-alpha-Hydroxylase Medicine(all) Mutation business.industry Biochemistry Genetics and Molecular Biology(all) Homozygote Infant General Medicine medicine.disease Arabs Pedigree Familial Hypophosphatemic Rickets Endocrinology Phenotype 1 25 dihydroxyvitamin D3 Dietary Supplements Calcium Female business |
| Zdroj: | BMC Research Notes |
| ISSN: | 1756-0500 |
| DOI: | 10.1186/1756-0500-7-783 |
| Popis: | 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. Case presentation 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). Conclusion 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. |
| Databáze: | OpenAIRE |
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