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Abstract #20631 Published in IGR 10-1
A novel de novo PAX6 mutation in an Ashkenazi-Jewish family with aniridia
Bandah D; Rosenmann A; Blumenfeld A; Averbukh E; Banin E; Sharon DMolecular Vision 2008; 14: 142-145
PURPOSE: To report a novel de novo PAX6 mutation in an Ashkenazi-Jewish family with autosomal dominant aniridia. METHODS: A mother and her daughter of Ashkenazi-Jewish origin were diagnosed with aniridia. Blood samples were drawn from family members and DNA was analyzed by direct sequencing and microsatellite marker analysis. RESULTS: The index patient and her daughter were affected with aniridia accompanied with congenital cataract, nystagmus, and glaucoma. A heterozygous PAX6 frameshift mutation in exon 6 (c.577_578insG, insGly72) was identified in the affected individuals and not in any of the unaffected family members including the parents of the index patient. Microsatellite analysis revealed that the index patient inherited the disease haplotype from her unaffected father. A sequence analysis of human PAX6 expressed sequence tags revealed the identification of spliced transcripts initiating from introns 4, 6, 7, 8, and 11. CONCLUSIONS: A novel de novo frameshift mutation in PAX6, which presumably occurred in the paternal gamete, was found in a family with autosomal dominant aniridia. The location of the mutation suggests that only full-length PAX6 isoforms would be disrupted, indicating that the normal expression of shorter, paired-less, protein isoforms cannot prevent manifestation of the disease.
Dr. D. Sharon, Department of Ophthalmology, Hadassah-Hebrew University Medical Center, POB 12000, Jerusalem 91120, Israel. Dror.sharon1@gmail.com
Classification:
9.4.3.5 Other (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders > 9.4.3 Glaucomas associated with disorders of the iris and ciliary body)
9.4.2.1 Iridocorneal endothelial syndrome (ICE, incl. irisatrophy) (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders > 9.4.2 Glaucomas associated with disorders of the cornea, conjunctiva, sclera)
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)