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J Pediatr Genet 2018; 07(02): 047-059
DOI: 10.1055/s-0038-1624577
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Genetics of Refractory Rickets: Identification of Novel PHEX Mutations in Indian Patients and a Literature Update

Binata Marik
1   Division of Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India
,
Arvind Bagga
2   Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India
,
Aditi Sinha
2   Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India
,
Pankaj Hari
2   Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India
,
Arundhati Sharma
1   Division of Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India
› Author Affiliations
Further Information

Publication History

03 August 2017

25 December 2017

Publication Date:
28 January 2018 (online)

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Abstract

Refractory rickets is a genetic disorder that cannot be treated by vitamin D supplementation and adequate dietary calcium and phosphorus. Hereditary hypophosphatemic rickets is one of the major forms of refractory rickets in Indian children and caused due to mutations in the PHEX, FGF23, DMP1, ENPP1, and SLC34A3 genes. This is the first study in India on a large number of patients reporting on mutational screening of the PHEX gene. Direct sequencing in 37 patients with refractory rickets revealed eight mutations in 13 patients of which 1 was nonsense, 2 were deletions, 1 was a deletion–insertion, and 4 were missense mutations. Of these mutations, four (c.566_567 delAG, c.651_654delACAT, c.1337delinsAATAA, and c.2048T > A) were novel mutations. This article discusses the mutations in Indian patients, collates information on the genetic causes of refractory rickets, and emphasizes the significance of genetic testing for precise diagnosis, timely treatment, and management of the condition, especially in developing countries.

Keywords

genetic disorder - hypophosphatemic rickets - PHEX - mutation - genetic testing
 

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