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Yelena Bykhovskaya, Kenneth Wright, Yaron Rabinowitz, Ana Laura Canedo; MIR184 c.57C>T mutation is responsible for congenital cataracts and corneal abnormalities in a five-generation family from Galicia, Spain. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1348.
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To identify genetic defect (s) in members of the five-generation family originated in Galicia, Spain with early onset cataracts and variable corneal abnormalities which include non-ectatic corneal thinning and severe early-onset keratoconus.
Family history was collected from the parents of a 9 year old boy with progressive loss of vision in both eyes due to congenital posterior cataracts and keratoconus. After it has identified additional affected family members thus suggesting a potential genetic nature of the boy’s condition, proband’s parents and his maternal and paternal grandmothers underwent a complete ophthalmological evaluation which included slit-lamp bioicroscope evaluation, retinoscopy, videokeratography, and OCT pachymetry measurements. We PCR amplified stem-loop region of MIR184 gene in the proband, his parents, and maternal grandmother. Amplified DNA was separated by agarose gel electrophoresis and correctly sized PCR product was sequenced using Sanger DNA sequencing. Sequence was confirmed by both forward and reverse sequencing.
We identified a heterozygous c.57C>T mutation in the stem loop of micro RNA-184 gene in the proband affected with bilateral congenital posterior cataract and keratoconus, his mother with bilateral cataracts and extremely thin corneas, and maternal grandmother (Figure). This is a same mutation that was earlier identified in both Northern Irish family with autosomal dominant keratoconus with early-onset anterior polar cataract and in family with autosomal dominant EDICT syndrome. Based on close genetic relationship between current inhabitants of Iberian Peninsula, especially Galicia, and Ireland, we suggest a single ancestral point of origin of this highly deleterious mutation in the family described in this study, Northern Irish family, and possibly EDICT family.
In this study we present only third known family with the c.57C>T MIRN184 mutation and variable abnormalities of the cornea and lens. We hypothesize that considerable differences in the clinical presentation should be attributed to the additional genetic modifier (s). We are working on establishing of an iPS cell model of MIRN184 defect in the proband and his mother which may shed some light on such modifier (s).
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