A novel pathogenic mutation of the CYP27B1 gene in a patient with vitamin D-dependent rickets type 1: a case report

BMC Research Notes

Hanan Ahmed Habib⁵  Ali Al Zahrani⁵  Ahmed Amer Al Boukai³  Ali Abdu N Al haboob²  Abdulrahman MH Al Nemri²  Nasir AM Al-Jurayyan⁴  Iman Al Gadi⁴  Amir MI Babiker¹ 

[1] Pediatric Department, College of Medicine, King Khalid University Hospital and King Saud University, PO Box 2925, Riyadh 11461, Saudi Arabia;Pediatric Department, College of Medicine and King Khalid University Hospital, Riyadh, Saudi Arabia;Radiology and Medical Imaging Department, King Khalid University Hospital and King Saud University, Riyadh, Saudi Arabia;Pediatric Endocrine Division, King Khalid University Hospital and King Saud University, Riyadh, Saudi Arabia;Pathology Department, King Khalid University Hospital and King Saud University, Riyadh, Saudi Arabia

关键词: VDDR-1;    Saudi Arabia;    Rickets;    Missense mutation;    1,25 dihydroxyvitamin D3;    CYP27B1;   

Others  :  1125710
DOI  :  10.1186/1756-0500-7-783

 received in 2014-08-24, accepted in 2014-10-24,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Babiker et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Hewison M, Zehnder D, Bland R, Stewart PM: 1 alpha-Hydroxylase and the action of vitamin D. J Mol Endocrinol 2000, 25:141-148.
• [2]Portale AA, Miller WL: Human 25-hydroxyvitamin D- 1 alpha-hydroxylase: cloning, mutations, and gene expression. Pediatr Nephrol 2000, 14:620-625.
• [3]Malloy PJ, Feldman D: Genetic disorders and defects in vitamin D action. Rheum Dis Clin North Am 2012, 38:93-106.
• [4]Allgrove J, Shaw N: Calcium and bone disorders in children and adolescents. In Endocrine Development. Volume 16. Basel: Karger AG; 2009.
• [5]Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW: Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci 2004, 101(20):7711-7715.
• [6]Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M, and on behalf of the Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society: Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics 2008, 122(2):398-417.
• [7]RefSeq: The NCBI Handbook [homepage on the Internet]. Chapter 18, The Reference Sequence (RefSeq) Project. c2013. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2002 [updated 2013 July 19; cited 2014 August 20] Available from: [http://www.ncbi.nlm.nih.gov/books/NBK21091/ webcite]
• [8]Wang JT, Lin CJ, Burridge SM, Fu GK, Labuda M, Portale AA, Miller WL: Genetics of vitamin D 1 alpha-hydroxylase deficiency in 17 families. Am J Hum Genet 1998, 63(6):1694-1702.
• [9]Griffiths AJF, Miller JH, Suzuki DT, Lewontin RC, Gelbart WM: An Introduction to Genetic Analysis. 7th edition. New York: W. H. Freeman; 2000.
• [10]Culbertson MR: RNA surveillance. Unforeseen consequences for gene expression, inherited genetic disorders and cancer. Trends Genet 1999, 15(2):74-80.
• [11]Wilkinson MF, Shyu AB: RNA surveillance by nuclear scanning? Nat Cell Biol 2002, 4(6):E144-E147.
• [12]Human Gene Mutation Database [homepage in the Internet] [cited 2014 August 20] Available from: [http://www.hgmd.cf.ac.uk/ webcite]