Exome sequencing can improve diagnosis and alter patient management

T. Dixon Salazar, J. Silhavy, N. Udpa, J. Schroth, S. Bielas, A. Schaffer, J. Olvera, V. Bafna, M. Zaki, G. Abdel Salam, L. Mansour, L. Selim, S. Abdel Hadi, N. Marzouki, T. Ben Omran, N. Al Saana, F. Sönmez, F. Celep, M. Azam, K. Hill, A. Collazo, A. Fenstermaker, G. Novarino, N. Akizu, K. Garimella, C. Sougnez, C. Russ, S. Gabriel, J. Gleeson, Science Translational Medicine 4 (2012).

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Abstract
The translation of "next-generation" sequencing directly to the clinic is still being assessed but has the potential for genetic diseases to reduce costs, advance accuracy, and point to unsuspected yet treatable conditions. To study its capability in the clinic, we performed whole-exome sequencing in 118 probands with a diagnosis of a pediatric-onset neurodevelopmental disease in which most known causes had been excluded. Twenty-two genes not previously identified as disease-causing were identified in this study (19% of cohort), further establishing exome sequencing as a useful tool for gene discovery. New genes identified included EXOC8 in Joubert syndrome and GFM2 in a patient with microcephaly, simplified gyral pattern, and insulin-dependent diabetes. Exome sequencing uncovered 10 probands (8% of cohort) with mutations in genes known to cause a disease different from the initial diagnosis. Upon further medical evaluation, these mutations were found to account for each proband's disease, leading to a change in diagnosis, some of which led to changes in patient management. Our data provide proof of principle that genomic strategies are useful in clarifying diagnosis in a proportion of patients with neurodevelopmental disorders.
Publishing Year
Date Published
2012-06-13
Journal Title
Science Translational Medicine
Volume
4
Issue
138
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Dixon Salazar T, Silhavy J, Udpa N, et al. Exome sequencing can improve diagnosis and alter patient management. Science Translational Medicine. 2012;4(138). doi:10.1126/scitranslmed.3003544
Dixon Salazar, T., Silhavy, J., Udpa, N., Schroth, J., Bielas, S., Schaffer, A., … Gleeson, J. (2012). Exome sequencing can improve diagnosis and alter patient management. Science Translational Medicine, 4(138). https://doi.org/10.1126/scitranslmed.3003544
Dixon Salazar, Tracy, Jennifer Silhavy, Nitin Udpa, Jana Schroth, Stephanie Bielas, Ashleigh Schaffer, Jesus Olvera, et al. “Exome Sequencing Can Improve Diagnosis and Alter Patient Management.” Science Translational Medicine 4, no. 138 (2012). https://doi.org/10.1126/scitranslmed.3003544.
T. Dixon Salazar et al., “Exome sequencing can improve diagnosis and alter patient management,” Science Translational Medicine, vol. 4, no. 138, 2012.
Dixon Salazar T, Silhavy J, Udpa N, Schroth J, Bielas S, Schaffer A, Olvera J, Bafna V, Zaki M, Abdel Salam G, Mansour L, Selim L, Abdel Hadi S, Marzouki N, Ben Omran T, Al Saana N, Sönmez F, Celep F, Azam M, Hill K, Collazo A, Fenstermaker A, Novarino G, Akizu N, Garimella K, Sougnez C, Russ C, Gabriel S, Gleeson J. 2012. Exome sequencing can improve diagnosis and alter patient management. Science Translational Medicine. 4(138).
Dixon Salazar, Tracy, et al. “Exome Sequencing Can Improve Diagnosis and Alter Patient Management.” Science Translational Medicine, vol. 4, no. 138, American Association for the Advancement of Science, 2012, doi:10.1126/scitranslmed.3003544.

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