Exome Sequencing in Monogenic Forms of Rickets

Objective To understand the phenotypic and genotypic spectrum of genetic forms of rickets in 10 families. Methods Detailed clinical, radiographic, and biochemical evaluation of 10 families with phenotypes suggestive of a genetic cause of rickets was performed. Molecular testing using exome sequencing aided in the diagnosis of six different forms of known genetic causes. Results Eleven disease-causing variants including five previously reported variants ( CYP27B1 :c.1319_1325dup, p.(Phe443Profs*24), VDR :c.1171C>T, p.(Arg391Cys), PHEX : c.1586_1586+1del, PHEX: c.1482+5G>C, PHEX: c.58C>T, p.(Arg20*)) and six novel variants ( CYP27B1 :c.974C>T, p.(Thr325Met), CYP27B1: c.1376G>A, p.(Arg459His), CYP2R1 : c.595C>T, p.(Arg199*), CYP2R1: c.1330G>C, p.(Gly444Arg), SLC34A3 :c.1336-11_1336-1del, SLC2A2 : c.589G>C, p.(Val197Leu)) in the genes known to cause monogenic rickets were identified. Conclusion The authors hereby report a case series of individuals from India with a molecular diagnosis of rickets and provide the literature review which would help in enhancing the clinical and molecular profile for rapid and differential diagnosis of rickets.