Abstract
To describe the utilization of Next Generation Sequencing technologies for genetic counseling and prenatal diagnosis. Ten families requested prenatal testing in view of previously affected offspring with genetically heterogeneous/hitherto undiagnosed disorders. Next generation sequencing was offered as a first tier investigation (1) in the probands who had not been diagnosed by baseline investigations, and (2) in cases where preliminary examination/testing suggested a genetically heterogeneous disorder, while the precise diagnosis was not available. The subsequently identified molecular basis enabled prenatal testing. The disorders included primary microcephaly, epidermolysis bullosa, inborn error of metabolism, infantile hypotonia, neuro-regression and sensorineural hearing loss. Five out of ten couples approached us during an ongoing pregnancy with two in the second trimester of gestation. Demise of the proband resulted in incomplete investigations in three cases. In seven cases, the disorder suspected was genetically heterogeneous and hence next generation testing was carried out while in the remaining three it was performed to ascertain the underlying gene involved. Fetal analysis detected recurrences in two cases, and the couples concerned decided to discontinue the pregnancies. Next generation sequencing proved a useful tool in select situations to overcome some of the challenges hindering a precise diagnosis in genetically heterogenous disorders.
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Acknowledgements
We sincerely thank Dr. Stephen Kingsmore and his team at the Children’s Mercy Hospital and Clinics, Kanas City, USA, Dr. VL Ramprasad at SciGenom, Centogene laboratories for analyzing the above cases via next generation sequencing. We also would like to thank Professor Yamaguchi at the department of Pediatrics, Shimane University School of Medicine, Shimane for helping us analyze the metabolites in the amniotic fluid. The research support from the Sir Ganga Ram Hospital is greatly acknowledged. We also want to thank all the patients and the families described in this study.
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Kotecha, U., Puri, R., Bijarnia, S. et al. Evaluating the Utility of Next Generation Sequencing Technology in the Diagnosis and Prevention of Genetic Disorders in India, the Early Experiences. J. Fetal Med. 6, 57–62 (2019). https://doi.org/10.1007/s40556-019-00204-y
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DOI: https://doi.org/10.1007/s40556-019-00204-y