Expanding the mutational spectrum of the ABCB4 gene in inherited adult cholestatic liver disorders with four novel pathogenic variants

Low phospholipid-associated cholelithiasis and intrahepatic cholestasis of pregnancy are two MDR3-related inherited liver disorders caused by biallelic or monoallelic ABCB4 loss-of-function variants. Low phospholipid-associated cholelithiasis is clinically characterized by the early onset of symptomatic cholelithiasis in young adults while intrahepatic cholestasis of pregnancy is a distinct clinical entity associated with adverse fetal outcomes. Of note, patients carrying ABCB4 sequence variations commonly exhibit phenotypic expression over a wide continuum due to environmental and hormonal contributing factors and genetic modifiers. Patients with an early diagnosis of MDR3-related diseases could benefit from ursodeoxycholic acid treatment in order to prevent acute and chronic complications as well as adverse pregnancy outcomes. We herein report five patients with an overlapping phenotype from low phospholipid-associated cholelithiasis to intrahepatic cholestasis of pregnancy, harboring five ABCB4 missense variants, four of which were novel. Our study highlights the phenotypic and genetic heterogeneity of inherited cholestatic liver diseases and also expands the mutation spectrum of ABCB4 sequence variations in adult cholestatic liver diseases

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Expanding the mutational spectrum of the ABCB4 gene in inherited adult cholestatic liver disorders with four novel pathogenic variants.

Low phospholipid-associated cholelithiasis and intrahepatic cholestasis of pregnancy are two MDR3-related inherited liver disorders caused by biallelic or monoallelic ABCB4 loss-of-function variants. Low phospholipid-associated cholelithiasis is clinically characterized by the early onset of symptomatic cholelithiasis in young adults while intrahepatic cholestasis of pregnancy is a distinct clinical entity associated with adverse fetal outcomes. Of note, patients carrying ABCB4 sequence variations commonly exhibit phenotypic expression over a wide continuum due to environmental and hormonal contributing factors and genetic modifiers. Patients with an early diagnosis of MDR3-related diseases could benefit from ursodeoxycholic acid treatment in order to prevent acute and chronic complications as well as adverse pregnancy outcomes. We herein report five patients with an overlapping phenotype from low phospholipid-associated cholelithiasis to intrahepatic cholestasis of pregnancy, harboring five ABCB4 missense variants, four of which were novel. Our study highlights the phenotypic and genetic heterogeneity of inherited cholestatic liver diseases and also expands the mutation spectrum of ABCB4 sequence variations in adult cholestatic liver diseases.

Scleral and corneal laceration with iris prolapse caused by an eagle claw.

BACKGROUND: To describe the visual rehabilitation after surgical treatment of an ocular injury sustained during an attack by a bird of prey. METHODS: A 51-year-old woman who was attacked by an eagle in a cage had a laceration of cornea and sclera at 9 o' clock, an iris prolapse that was jammed into the scleral wound, and a flat anterior chamber with hyphema. The uncorrected visual acuity was hand movements. Surgical treatment was performed immediately and included iris repositioning and suturing, scleral and conjunctival suturing, and transscleral cryotherapy to the retina. RESULTS: Eight months later, the best corrected visual acuity was 20/20. The anterior segment showed a posterior synechia in the area of the iris repair and an almost round pupil; the crystalline lens showed only a localized opacification. CONCLUSIONS: A bird of prey, even though caged, can injure an eye in humans. With immediate surgical treatment, good visual rehabilitation was achieved in this case. It should be reiterated that spectacles offer no protection against ocular trauma in these cases.