Personalized genomic medicine: lessons from the exome - PubMed (original) (raw)

Case Reports

. 2011 Sep-Oct;104(1-2):189-91.

doi: 10.1016/j.ymgme.2011.06.022. Epub 2011 Jul 5.

Daniel E Pineda-Alvarez, Donald W Hadley, NISC Comparative Sequencing Program, Jamie K Teer, Praveen F Cherukuri, Nancy F Hansen, Pedro Cruz, Alice C Young, Robert W Blakesley, Brendan Lanpher, Stephanie Mayfield Gibson, Murat Sincan, Settara C Chandrasekharappa, James C Mullikin

Affiliations

Case Reports

Personalized genomic medicine: lessons from the exome

Benjamin D Solomon et al. Mol Genet Metab. 2011 Sep-Oct.

Abstract

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.

Published by Elsevier Inc.

PubMed Disclaimer

Figures

Fig.

Fig.

Hypothesized explanation for pulmonary artery hypertension in the patient described here[–12, 14]. A loss-of-function mutation in the CPSI gene (1) leads to impaired production of citrulline (2) and arginine (3). The lack of availability of these precursors leads to decreased availability of nitric oxide (4), resulting in decreased pulmonary artery vasodilation, which becomes especially severe in concert with iatrogenic depletion of arginine and citrulline.

Similar articles

Cited by

References

    1. Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ. Exome sequencing identifies the cause of a mendelian disorder. Nat. Genet. 2010;42:30–35. - PMC - PubMed
    1. Teer JK, Mullikin JC. Exome sequencing: the sweet spot before whole genomes. Hum. Mol. Genet. 2010;19:R145–R151. - PMC - PubMed
    1. Tucker T, Marra M, Friedman JM. Massively parallel sequencing: the next big thing in genetic medicine. Am. J. Hum. Genet. 2009;85:142–154. - PMC - PubMed
    1. Quan L, Smith DW. The VATER association. Vertebral defects, Anal atresia, T-E fistula with esophageal atresia, Radial and Renal dysplasia: a spectrum of associated defects. J. Pediatr. 1973;82:104–107. - PubMed
    1. Solomon BD, Pineda-Alvarez DE, Raam MS, Bous SM, Keaton AA, Velez JI, Cummings DA. Analysis of component findings in 79 patients diagnosed with VACTERL association. Am. J. Med. Genet. A. 2010;152A:2236–2244. - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources