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James A. Eadie, John Hart, Les Siegel; Genetic Analysis of a Family with a Novel Type I Fibrillinopathy. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1564.
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© ARVO (1962-2015); The Authors (2016-present)
To describe a novel polymorphism in the Fibrillin gene (FBN1) and the associated unique Type I Fibrillinopathy phonotypic variant found in a single family.
The proband of the study was identified in clinic after referral from an outside institution for ectopia lentis (EL). Following a careful family history that was remarkable for several other family members with zonular instability detected at the time of cataract surgery, the patient was sent for evaluation by the department of genetics at William Beaumont Hospital. A thorough workup for known causes of ectopia lentis uncovered a novel polymorphism in the FBN1 gene (c.730T>C). A pedigree was devised and, after approval by the Human Investigations Committee at William Beaumont Hospital, medical records and prospective genetic testing was obtained on eight additional family members.
The misprint mutation c.730T>C in the FBN1 gene was detected in all three family members with confirmed ectopia lentis at the time of cataract surgery. This misprint mutation resulted in a change from cysteine to arginine at amino acid position 244. In addition, this misprint was detected in 3 of 6 offspring of known carriers who had not yet undergone cataract surgery.
In our genotypic and phenotypic analysis of this single family we describe a novel misprint mutation in FBN1. Because none of the family member fit the Ghent criteria for Marfan Syndrome the established diagnosis associated with this genetic presentation is Type I Fibrillinopathy. This phenotypic presentation is unique in that, although there have been reports of isolated ectopia lentis associated with FBN1 mutations, the zonular insufficiency in this family does not manifest until the time of cataract surgery. The presence of this disease entity provides a possible explanation for idiopathic zonular weakness encountered in what is expected to be routine ocular surgery.
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