Novel and de-novo truncating PAX6 mutations and ocular phenotypes in Thai aniridia patients.
OBJECTIVE
To describe the ophthalmic findings and mutation analyses of the PAX6 gene in Thai aniridia patients.


METHODS
Ten patients from six unrelated families underwent a comprehensive ophthalmic examination. Mutations in the PAX6 gene were screened by single-strand conformational polymorphism (SSCP) and direct DNA sequencing of the SSCP variants.


RESULTS
Seven patients developed cataracts and six developed glaucoma. Mutation analysis demonstrated four different truncating mutations, two of which were de novo. These included one novel insertion/deletion mutation (c.474del12insGA in exon 5) and three nonsense mutations. R203X and R240X are common recurrent mutations, while Q277X in exon 10 is novel. All mutations resulted in loss of function of the PAX6 protein.


CONCLUSIONS
Our data confirm inter- and intrafamilial variable phenotypic manifestations of which the underlying mechanisms may be haploinsufficiency or dominant-negative mutation.
Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok Road, Bangkok-noi, Bangkok 10700, Thailand. atchanee@hotmail.com
La-Ongsri
LO
Atchaneeyasakul
Adisak
A
Trinavarat
Dhaivadee
D
Dulayajinda
Kornphet
K
Kumpornsin
Wanna
W
Thongnoppakhun
Pa-thai
PT
Yenchitsomanus
Chanin
C
Limwongse
D000293:Adolescent; D000328:Adult; D000368:Aged; D015783:Aniridia / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis; D005123:Eye / Q000378:metabolism / Q000473:pathology*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012097:Repressor Proteins / Q000235:genetics*; D017384:Sequence Deletion; D013785:Thailand; D014792:Visual Acuity / Q000235:genetics*
D018389:Codon, Nonsense; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins