title: Discordant clinical phenotype in monozygotic twins with Alagille syndrome: Possible influence of non-genetic factors.
abstract: Alagille syndrome is a multisystem developmental disorder characterized by bile duct paucity, congenital heart disease, vertebral anomalies, posterior embryotoxon, and characteristic facial features. Alagille syndrome is typically the result of germline mutations in JAG1 or NOTCH2 and is one of several human diseases caused by Notch signaling abnormalities. A wide phenotypic spectrum has been well documented in Alagille syndrome. Therefore, monozygotic twins with Alagille syndrome provide a unique opportunity to evaluate potential phenotypic modifiers such as environmental factors or stochastic effects of gene expression. In this report, we describe an Alagille syndrome monozygotic twin pair with discordant placental and clinical findings. We propose that environmental factors such as prenatal hypoxia may have played a role in determining the phenotypic severity.
authors.affiliation: Division of Medical Genetics, Nagano Children's Hospital, Azumino, Japan.|Research Center for Epigenetic Disease, Institute for Molecular and Cellular Biosciences, the University of Tokyo, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Izumi
authors.affiliation: Division of Medical Genetics, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hayashi
authors.affiliation: Department of Pathology and Laboratory Medicine, the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Grochowski
authors.affiliation: Department of Laboratory Medicine, Nagano Children's Hospital, Azumino, Japan.|Life Science Research Center, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kubota
authors.affiliation: Division of Medical Genetics, Nagano Children's Hospital, Azumino, Japan.|Life Science Research Center, Nagano Children's Hospital, Azumino, Japan.|Department of Medical Genetics, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Nishi
authors.affiliation: Division of Medical Genetics, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Arakawa
authors.affiliation: Division of Neonatology, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Hiroma
authors.affiliation: Department of Pediatric Surgery, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hatata
authors.affiliation: Division of Clinical Pathology, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ogiso
authors.affiliation: Life Science Research Center, Nagano Children's Hospital, Azumino, Japan.|Division of Neonatology, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Pathology and Laboratory Medicine, the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Falsey
authors.affiliation: Department of Laboratory Medicine, Nagano Children's Hospital, Azumino, Japan.|Life Science Research Center, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Eiko
authors.initials: E
authors.lastname: Hidaka
authors.affiliation: Department of Pathology and Laboratory Medicine, the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Spinner
mesh_terms: D000328:Adult; D016738:Alagille Syndrome / Q000175:diagnosis* / Q000209:etiology; D002135:Calcium-Binding Proteins / Q000235:genetics; D004777:Environment; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000150:complications*; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010920:Placenta / Q000473:pathology*; D011247:Pregnancy; D000072099:Serrate-Jagged Proteins; D014430:Twins, Monozygotic
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D000072099:Serrate-Jagged Proteins
keywords: Notch signaling; SNP array; monozygotic twin