TY - JOUR
T1 - Exome Sequencing in Monogenic Forms of Rickets
AU - Jacob, Prince
AU - Bhavani, Gandham Sri Lakshmi
AU - Udupa, Prajna
AU - Wang, Zheng
AU - Hariharan, Sankar V.
AU - Delampady, Kishan
AU - Dalal, Ashwin
AU - Kamath, Nutan
AU - Ikegawa, Shiro
AU - Shenoy, Rathika D.
AU - Handattu, Koushik
AU - Shah, Hitesh
AU - Girisha, Katta M.
N1 - Funding Information:
Open access funding provided by Manipal Academy of Higher Education, Manipal. This study was supported by the following: Department of Science and Technology, Government of India funded the project entitled ‘Application of Autozygosity Mapping and Exome Sequencing to Identify Genetic Basis of Disorders of Skeletal Development’ (SB/SO/HS/005/2014) to Katta M. Girisha and Department of Biotechnology, Government of India funded the project entitled ‘Development of Genomic Technologies for Predictive Genetic Health and Forensic Profiling’ (Grant No. BTl/AAQ/01/CDFD-Flagship/2019) to Ashwin Dalal. This study was also supported partially by DBT/Wellcome Trust India Alliance Fellowship (India Alliance) under the project entitled ‘Center for Rare Disease Diagnosis, Research and Training’ (Grant ID: GR-0011; Reference number: IA/ CRC/20/1/600002) awarded to Katta M. Girisha.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85146745198
UR - https://www.scopus.com/pages/publications/85146745198#tab=citedBy
U2 - 10.1007/s12098-022-04393-9
DO - 10.1007/s12098-022-04393-9
M3 - Article
C2 - 36692815
AN - SCOPUS:85146745198
SN - 0019-5456
VL - 90
SP - 1182
EP - 1190
JO - Indian Journal of Pediatrics
JF - Indian Journal of Pediatrics
IS - 12
ER -