TY - JOUR
T1 - Novel mutations in NOTCH2 gene in infants with neonatal cholestasis
AU - Shaul, Eliana
AU - Kogan-Liberman, Debora
AU - Schuckalo, Stephanie
AU - Jan, Dominique
AU - Ewart, Michelle
AU - Nguyen, Trang
AU - Martinez, Mercedes
AU - Ovchinsky, Nadia
N1 - Publisher Copyright:
©Copyright: the Author(s), 2019.
PY - 2019
Y1 - 2019
N2 - One cause of neonatal cholestasis (NC) is paucity of intrahepatic bile ducts which can be associated with Alagille syndrome or non- syndromic. Alagille syndrome is caused by autosomal dominant mutations in the Notch signaling pathway ligand Jagged1 in 94% of patients and mutations in the NOTCH2 receptor in <1% of patients. This is a retrospective case series studying infants with neonatal cholestasis found to have variants of unknown significance (VOUS) in NOTCH2. Sorting intolerant from tolerant (SIFT) and polymorphism phenotyping (PolyPhen) were utilized to predict a damaging effect. Five infants with NC without other features of Alagille syndrome were found to have one copy of a VOUS in NOTCH2, predicted to be damaging by SIFT and PolyPhen. Our cases support the notion that NOTCH2 mutations may result in hypoplastic biliary system. Further characterization of these variants is important to assist with our clinical approach to NC.
AB - One cause of neonatal cholestasis (NC) is paucity of intrahepatic bile ducts which can be associated with Alagille syndrome or non- syndromic. Alagille syndrome is caused by autosomal dominant mutations in the Notch signaling pathway ligand Jagged1 in 94% of patients and mutations in the NOTCH2 receptor in <1% of patients. This is a retrospective case series studying infants with neonatal cholestasis found to have variants of unknown significance (VOUS) in NOTCH2. Sorting intolerant from tolerant (SIFT) and polymorphism phenotyping (PolyPhen) were utilized to predict a damaging effect. Five infants with NC without other features of Alagille syndrome were found to have one copy of a VOUS in NOTCH2, predicted to be damaging by SIFT and PolyPhen. Our cases support the notion that NOTCH2 mutations may result in hypoplastic biliary system. Further characterization of these variants is important to assist with our clinical approach to NC.
KW - NOTCH2
KW - Neonatal Cholestasis
KW - Paucity of intrahepatic bile ducts
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U2 - 10.4081/pr.2019.8206
DO - 10.4081/pr.2019.8206
M3 - Article
AN - SCOPUS:85090677125
SN - 2036-749X
VL - 11
SP - 53
EP - 55
JO - Pediatric Reports
JF - Pediatric Reports
IS - 3
ER -