title: Whole-exome sequencing reveals GPIHBP1 mutations in infantile colitis with severe hypertriglyceridemia.
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.
authors.affiliation: *Department of Molecular and Human Genetics †Department of Pediatrics ‡Human Genome Sequencing Center §Section of Pediatric Pathology, Department of Pathology, Baylor College of Medicine, Houston, TX.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gonzaga-Jauregui
authors.forename: Sabina
authors.initials: S
authors.lastname: Mir
authors.forename: Samantha
authors.initials: S
authors.lastname: Penney
authors.forename: Shalini
authors.initials: S
authors.lastname: Jhangiani
authors.forename: Craig
authors.initials: C
authors.lastname: Midgen
authors.forename: Milton
authors.initials: M
authors.lastname: Finegold
authors.forename: Donna M
authors.initials: DM
authors.lastname: Muzny
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Bacino
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.forename: Richard
authors.initials: R
authors.lastname: Kellermayer
authors.forename: Neil A
authors.initials: NA
authors.lastname: Hanchard
mesh_terms: D003092:Colitis / Q000150:complications*; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics*; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000150:complications / Q000151:congenital / Q000235:genetics*; D007223:Infant; D018110:Receptors, Lipoprotein / Q000235:genetics*
chemical_list: C523701:GPIHBP1 protein, human; D018110:Receptors, Lipoprotein