TY - JOUR
T1 - Personalized genomic medicine
T2 - Lessons from the exome
AU - Solomon, Benjamin D.
AU - Pineda-Alvarez, Daniel E.
AU - Hadley, Donald W.
AU - Teer, Jamie K.
AU - Cherukuri, Praveen F.
AU - Hansen, Nancy F.
AU - Cruz, Pedro
AU - Young, Alice C.
AU - Blakesley, Robert W.
AU - Lanpher, Brendan
AU - Mayfield Gibson, Stephanie
AU - Sincan, Murat
AU - Chandrasekharappa, Settara C.
AU - Mullikin, James C.
N1 - Funding Information:
This research was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health . We would like to extend our gratitude to the family for participating in this study. Sanger sequencing support was provided by the core DNA sequencing facility, National Institute of Neurological Disorders and Stroke. We would like to thank Dr. William A. Gahl for use of data (collected through the National Institutes of Health Undiagnosed Diseases Program) as controls. We would also like to thank Dr. Maximilian Muenke for his mentoring and support.
PY - 2011/9/1
Y1 - 2011/9/1
N2 - While genomic sequencing methods are powerful tools in the discovery of the genetic underpinnings of human disease, incidentally-revealed novel genomic risk factors may be equally important, both scientifically, and as relates to direct patient care. We performed whole-exome sequencing on a child with VACTERL association who suffered severe post-surgical neonatal pulmonary hypertension, and identified a potential novel genetic risk factor for this complication: a heterozygous mutation in CPSI. Newborn screening results from this patient's monozygotic twin provided evidence that this mutation, in combination with an environmental trigger (in this case, surgery), may have resulted in pulmonary artery hypertension due to inadequate nitric oxide production. Identification of this genetic risk factor allows for targeted medical preventative measures in this patient as well as relatives with the same mutation, and illustrates the power of incidental medical information unearthed by whole-exome sequencing.
AB - While genomic sequencing methods are powerful tools in the discovery of the genetic underpinnings of human disease, incidentally-revealed novel genomic risk factors may be equally important, both scientifically, and as relates to direct patient care. We performed whole-exome sequencing on a child with VACTERL association who suffered severe post-surgical neonatal pulmonary hypertension, and identified a potential novel genetic risk factor for this complication: a heterozygous mutation in CPSI. Newborn screening results from this patient's monozygotic twin provided evidence that this mutation, in combination with an environmental trigger (in this case, surgery), may have resulted in pulmonary artery hypertension due to inadequate nitric oxide production. Identification of this genetic risk factor allows for targeted medical preventative measures in this patient as well as relatives with the same mutation, and illustrates the power of incidental medical information unearthed by whole-exome sequencing.
KW - CPSI
KW - Pulmonary artery hypertension
KW - VACTERL
KW - Whole-exome sequencing
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U2 - 10.1016/j.ymgme.2011.06.022
DO - 10.1016/j.ymgme.2011.06.022
M3 - Article
C2 - 21767969
AN - SCOPUS:80052521660
SN - 1096-7192
VL - 104
SP - 189
EP - 191
JO - Biochemical Medicine and Metabolic Biology
JF - Biochemical Medicine and Metabolic Biology
IS - 1-2
ER -