Discordant clinical phenotype in monozygotic twins with Alagille syndrome: Possible influence of non-genetic factors

作者：Izumi Kosuke^*; Hayashi Daisuke; Grochowski Christopher M; Kubota Noriko; Nishi Eriko; Arakawa Michiko; Hiroma Takehiko; Hatata Tomoko; Ogiso Yoshifumi; Nakamura Tomohiko; Falsey Alexandra M; Hidaka Eiko; Spinner Nancy B

来源：American Journal of Medical Genetics, Part A, 2016, 170(2): 471-475.

DOI：10.1002/ajmg.a.37429

• SNP array
• monozygotic twin
• Notch signaling

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.

• 出版日期2016-2