A novel de novo PAX6 mutation in an Ashkenazi-Jewish family with aniridia.
OBJECTIVE
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 by congenital cataract, nystagmus, and glaucoma. A heterozygous PAX6 frameshift mutation in exon 6 (c.577_578insG, insG@Gly72) 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.
Bandah
Dikla
D
Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Rosenmann
Ada
A
Blumenfeld
Anat
A
Averbukh
Edward
E
Banin
Eyal
E
Sharon
Dror
D
D000595:Amino Acid Sequence; D015783:Aniridia / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D020224:Expressed Sequence Tags; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics; D007585:Jews / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics*
D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins