title: Novel liver findings in ornithine transcarbamylase deficiency due to Xp11.4-p21.1 microdeletion.
abstract: Ornithine transcarbamylase deficiency (OTCD, OMIM 311250), the most common urea cycle disorder, results in impaired synthesis of citrulline from carbamoyl phosphate and ornithine. Individuals have been identified with OTCD due to a contiguous gene deletion at Xp11.4-p21.1 and unique clinical features, described as the "extended OTCD phenotype". We present a male with neonatal-lethal OTCD due to a 1.87Mb microdeletion at Xp11.4-p21.1 (37126841-38998991 hg18). Autopsy revealed a novel histological finding of hepatocyte globular and granular inclusions. Such inclusions have not been described in OTCD or other metabolic disorders and are not an associated finding in neonatal liver failure due to other causes. The deleted region includes the gene SYTL5, potentially involved in RAB27A-dependent membrane trafficking in the liver and placenta. We propose that the contiguous gene deletion could contribute to the severity of the clinical presentation here and hypothesize that deletion of SYTL5 could contribute to the liver findings.
authors.affiliation: Departments of Pediatrics and Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Gallant
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, UCLA Clinical Genomics Center, Los Angeles, California.
authors.forename: Dorina
authors.initials: D
authors.lastname: Gui
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, UCLA Clinical Genomics Center, Los Angeles, California.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Lassman
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, UCLA Clinical Genomics Center, Los Angeles, California.
authors.forename: William H
authors.initials: WH
authors.lastname: Yong
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, UCLA Clinical Genomics Center, Los Angeles, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Teitell
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA.
authors.forename: Diana
authors.initials: D
authors.lastname: Mandelker
authors.affiliation: Genetic Disease Screening Program, California Department of Public Health, Richmond, CA, USA.
authors.forename: Fred
authors.initials: F
authors.lastname: Lorey
authors.affiliation: Departments of Pediatrics and Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California. Electronic address: julianmartinez@mednet.ucla.edu.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Martinez-Agosto
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, UCLA Clinical Genomics Center, Los Angeles, California. Electronic address: fquintero@mednet.ucla.edu.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Quintero-Rivera
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X; D006801:Humans; D007231:Infant, Newborn; D008099:Liver / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000235:genetics* / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; C457772:SYTL5 protein, human
keywords: Chromosomal microarray analysis; Hepatocyte inclusions; OTCD; Ornithine transcarbamylase deficiency; Post-analytical tool; SYTL5; Xp11.4, Xp21.1 deletion; Xp11.4-p21.1