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 1.87. Mb 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 249-253 |
| Number of pages | 5 |
| Journal | Gene |
| Volume | 556 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 1 2015 |
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Keywords
- Chromosomal microarray analysis
- Hepatocyte inclusions
- Ornithine transcarbamylase deficiency
- OTCD
- Post-analytical tool
- SYTL5
- Xp11.4, Xp21.1 deletion
- Xp11.4-p21.1
ASJC Scopus subject areas
- Genetics
Cite this
Novel liver findings in Ornithine Transcarbamylase Deficiency due to Xp11.4-p21.1 microdeletion. / Gallant, Natalie M.; Gui, Dorina; Lassman, Charles R.; Yong, William H.; Teitell, Michael; Mandelker, Diana; Lorey, Fred; Martinez-Agosto, Julian A.; Quintero-Rivera, Fabiola.
In: Gene, Vol. 556, No. 2, 01.01.2015, p. 249-253.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Novel liver findings in Ornithine Transcarbamylase Deficiency due to Xp11.4-p21.1 microdeletion
AU - Gallant, Natalie M.
AU - Gui, Dorina
AU - Lassman, Charles R.
AU - Yong, William H.
AU - Teitell, Michael
AU - Mandelker, Diana
AU - Lorey, Fred
AU - Martinez-Agosto, Julian A.
AU - Quintero-Rivera, Fabiola
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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 1.87. Mb 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.
AB - 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 1.87. Mb 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.
KW - Chromosomal microarray analysis
KW - Hepatocyte inclusions
KW - Ornithine transcarbamylase deficiency
KW - OTCD
KW - Post-analytical tool
KW - SYTL5
KW - Xp11.4, Xp21.1 deletion
KW - Xp11.4-p21.1
UR - http://www.scopus.com/inward/record.url?scp=84919623565&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84919623565&partnerID=8YFLogxK
U2 - 10.1016/j.gene.2014.11.057
DO - 10.1016/j.gene.2014.11.057
M3 - Article
C2 - 25434494
AN - SCOPUS:84919623565
VL - 556
SP - 249
EP - 253
JO - Gene
JF - Gene
SN - 0378-1119
IS - 2
ER -