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.

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.

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