Whole-Exome Sequencing Reveals GPIHBP1 Mutations in Infantile Colitis With Severe Hypertriglyceridemia
Claudia Gonzaga-Jauregui
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
Search for more papers by this authorSabina Mir
Department of Pediatrics, Baylor College of Medicine, Houston, TX
Search for more papers by this authorSamantha Penney
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
Search for more papers by this authorShalini Jhangiani
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX
Search for more papers by this authorCraig Midgen
Section of Pediatric Pathology, Department of Pathology, Baylor College of Medicine, Houston, TX
Search for more papers by this authorMilton Finegold
Section of Pediatric Pathology, Department of Pathology, Baylor College of Medicine, Houston, TX
Search for more papers by this authorDonna M. Muzny
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX
Search for more papers by this authorMin Wang
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX
Search for more papers by this authorCarlos A. Bacino
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
Search for more papers by this authorRichard A. Gibbs
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
Search for more papers by this authorJames R. Lupski
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
Search for more papers by this authorRichard Kellermayer
Department of Pediatrics, Baylor College of Medicine, Houston, TX
Search for more papers by this authorCorresponding Author
Neil A. Hanchard
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
Address correspondence and reprint requests to Neil A. Hanchard, MD, PhD, Baylor College of Medicine, Houston, TX (e-mail: [email protected]).Search for more papers by this authorClaudia Gonzaga-Jauregui
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
Search for more papers by this authorSabina Mir
Department of Pediatrics, Baylor College of Medicine, Houston, TX
Search for more papers by this authorSamantha Penney
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
Search for more papers by this authorShalini Jhangiani
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX
Search for more papers by this authorCraig Midgen
Section of Pediatric Pathology, Department of Pathology, Baylor College of Medicine, Houston, TX
Search for more papers by this authorMilton Finegold
Section of Pediatric Pathology, Department of Pathology, Baylor College of Medicine, Houston, TX
Search for more papers by this authorDonna M. Muzny
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX
Search for more papers by this authorMin Wang
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX
Search for more papers by this authorCarlos A. Bacino
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
Search for more papers by this authorRichard A. Gibbs
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
Search for more papers by this authorJames R. Lupski
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
Search for more papers by this authorRichard Kellermayer
Department of Pediatrics, Baylor College of Medicine, Houston, TX
Search for more papers by this authorCorresponding Author
Neil A. Hanchard
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
Address correspondence and reprint requests to Neil A. Hanchard, MD, PhD, Baylor College of Medicine, Houston, TX (e-mail: [email protected]).Search for more papers by this authorDrs Gonzaga-Jauregui and Mir contributed equally to the work.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org).
This work was supported by grant U54HG006542 from the National Human Genome Research Institute (NHGRI) to the Baylor-Hopkins Center for Mendelian Genomics.
J.R.L. is supported by grants R01NS058529 from the National Institute of Neurological Disorders and Stroke and U54HG006542 from the National Human Genome Research Institute and is a consultant for Athena Diagnostics, 23andMe, and Ion Torrent Systems, Inc and holds multiple US and European patents for DNA diagnostics. R.A.G. is supported by the National Human Genome Research Institute grant 2-U54HG003273-09 and the National Cancer Institute, was an owner of SeqWright, and is an advisor to GE Healthcare/Clarient and the Allen Institute for Brain Science. N.A.H. is supported by a Clinical Scientist Development Award from the Doris Duke Charitable Foundation. The other authors report no conflicts of interest.
ABSTRACT
Severe congenital hypertriglyceridemia (HTG) is a rare disorder caused by mutations in genes affecting lipoprotein lipase (LPL) activity. Here we report a 5-week-old Hispanic girl with severe HTG (12,031 mg/dL, normal limit 150 mg/dL) who presented with the unusual combination of lower gastrointestinal bleeding and milky plasma. Initial colonoscopy was consistent with colitis, which resolved with reduction of triglycerides. After negative sequencing of the LPL gene, whole-exome sequencing revealed novel compound heterozygous mutations in GPIHBP1. Our study broadens the phenotype of GPIHBP1-associated HTG, reinforces the effectiveness of whole-exome sequencing in Mendelian diagnoses, and implicates triglycerides in gastrointestinal mucosal injury.
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