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Mircea N. Coca, Mohamed Soliman, Emmanuel Chang, Genetics; Concomitant presentation of novel mutations in NDP and LRP5 genes in a patient with suspected Norrie and FEVR diseases. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2872.
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© ARVO (1962-2015); The Authors (2016-present)
To describe the clinical manifestation and genetic analysis of a patient with concomitant Norrie disease and Familial Exudative Vitreoretinopathy (FEVR) disease spectrum caused by two novel mutations in NDP and LRP5 genes, respectively.
We report the case of a 6 weeks old full term Hispanic male who presented after his pediatrician noticed poor red reflexes bilaterally and a mildly enlarged left eye. A complete ophthalmologic examination was performed. The left eye exam was significant for proptosis, corectopia, elevated IOP, haziness and enlarged diameter of the left cornea. There were bilateral yellow, vascular membranes obscuring the view of the posterior segment. B scan ultrasound showed bilateral hyperechoic lesions connecting the posterior lens surface to the optic nerve head. Intraocular pressures measured 11 mmHg OD and 31 mmHg OS during an exam under anesthesia and handheld slit lamp examination showed shallow anterior chambers, prominent radial iris blood vessels, and posterior synechia bilaterally, with more advanced changes in the left eye. A Visual Evoked Potential test showed abnormal, extinguished responses to flash stimuli with cortical areas 17, 18, and 19 functional impairing. Hearing tests showed adequate hearing levels.
The chromosomal analysis established two novel gene mutations. The first is a hemizygous nonsense mutation c.211C>T (p.Q71*) in the exon 3 of X-linked NDP gene; other nonsense mutations have been reported on this exon in patients with Norrie disease.<br /> The second is a homozygous unclassified mutation c.1130C>T (p.A377V) in the LRP5 gene. The alanine at amino acid position 377 of the LRP5 protein is highly conserved during evolution, so significance of this variant is currently unclear.<br /> Targeted parental sequence analyses indicates that the patient inherited c.1130C>T in the LRP5 gene from his asymptomatic father. The patient’s mother tested negative for any relevant mutations. Also a maternal uncle had a history of premature delivery, mental retardation, hearing loss and blindness requiring retina surgery, and glaucoma diagnosed just after birth.
This is the first case reporting on two new concomitant mutations, one on X-linked NDP gene and the other LRP5 gene located on chromosome 11. LRP5 gene mutation is in a highly conserved region and its significance is currently unclear.
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