Marfan syndrome caused by a novel FBN1 mutation with associated pigmentary glaucoma
John Kuchtey1, Ta Chen Chang, Lampros Panagis
1Vanderbilt Eye Institute, Vanderbilt University, Nashville, TN 37232, USA.
Abstract:
Mutations in fibrillin-1 (FBN1) cause a wide spectrum of disorders, including Marfan syndrome, which have in common defects in fibrillin-1 microfibrils. Ectopia lentis and myopia are frequently observed ocular manifestations of Marfan syndrome. Glaucoma is also associated with Marfan syndrome, though the form of glaucoma has not been well-characterized. In this report, ocular examination of a patient diagnosed with Marfan syndrome based on family history and aortic dilatation was performed, including measurement of facility of aqueous humor outflow by tonography. The patient did not have ectopia lentis at the age of 42 years. Based on optic nerve appearance, reduced outflow facility, elevated IOP with open angles and clear signs of pigment dispersion, the patient was diagnosed with pigmentary glaucoma. The patient was heterozygous for a novel truncating mutation in FBN1, p.Leu72Ter. Histology of normal human eyes revealed abundant expression of elastic fibers and fibrillin-1 in aqueous humor outflow structures. This is the first report of a patient with Marfan syndrome that is caused by a confirmed FBN1 mutation with associated pigmentary glaucoma. In addition to identifying a novel mutation of FBN1 and broadening the spectrum of associated ocular phenotypes in Marfan syndrome, our findings suggest that pigmentary glaucoma may involve defects in fibrillin-1 microfibrils.
Insights
Marfan syndrome, caused by fibrillin-1 (FBN1) mutations, can lead to pigmentary glaucoma. This study identified a novel FBN1 mutation in a patient with Marfan syndrome and pigmentary glaucoma, suggesting microfibril defects contribute to this eye condition.
Area of Science:
- Ophthalmology
- Genetics
- Connective Tissue Disorders
Background:
- Mutations in the fibrillin-1 (FBN1) gene cause Marfan syndrome, characterized by defects in fibrillin-1 microfibrils.
- Ocular manifestations like ectopia lentis and myopia are common in Marfan syndrome, but glaucoma's specific form remains unclear.
- Fibrillin-1 is crucial for the structural integrity of ocular tissues.
Observation:
- A 42-year-old patient with Marfan syndrome and aortic dilatation presented with elevated intraocular pressure (IOP), reduced aqueous humor outflow facility, and signs of pigment dispersion.
- The patient did not exhibit ectopia lentis but was diagnosed with pigmentary glaucoma based on ocular examination and tonography.
Findings:
- A novel truncating mutation in FBN1 (p.Leu72Ter) was identified in the patient, confirming a genetic link to Marfan syndrome.
- Histological examination of normal human eyes showed abundant fibrillin-1 in structures crucial for aqueous humor outflow.
Implications:
- This is the first report linking a confirmed FBN1 mutation in Marfan syndrome to pigmentary glaucoma.
- The findings suggest that fibrillin-1 microfibril defects may play a role in the pathogenesis of pigmentary glaucoma, expanding the known ocular phenotypes of FBN1 mutations.
More Related Videos
06:27Müller Glia Cell Activation in a Laser-induced Retinal Degeneration and Regeneration Model in Zebrafish
Published on: October 27, 2017
07:04Electroporation-Based Genetic Modification of Primary Human Pigment Epithelial Cells Using the Sleeping Beauty Transposon System
Published on: February 4, 2021
Related Concept Videos
Glaucoma: Overview
Open Angle Glaucoma: Treatment
Drugs such as carbonic anhydrase inhibitors, α2- and...
Angle Closure Glaucoma: Treatment
Photoreceptors and Visual Pathways
Genetic Lingo
Prosopagnosia
