title: Investigation of a PAX6 gene mutation in a Malaysian family with congenital aniridia.
abstract: Mutations in the PAX6 gene that cause aniridia have been identified in various ethnicities but not in the Malaysian population. Therefore, the objective of this study was to investigate the PAX6 mutation in a Malaysian family with congenital aniridia. In this study, a complete ophthalmic examination was performed on a Dusun ethnic family with aniridia. Genomic DNA was extracted from the peripheral blood of the subjects and screened for the PAX6 gene mutation using polymerase chain reaction amplification high-resolution melting curve analysis (PCR-HRM) followed by confirmation via direct DNA sequencing. A heterozygous G deletion (c.857delG) in exon 7 causing a frame shift in PAX6 was identified in all affected family members. Genotype-phenotype correlation analysis revealed congenital cataract and all affected family members showed a similar spectrum of aniridia with no phenotypic variability but with differences in severity that were age-dependent. In summary, by using a PCR-HRM approach, this study is the first to report a PAX6 mutation in a Malaysian family. This mutation is the cause of the aniridia spectra observed in this family and of congenital cataract.
authors.affiliation: School of Science and Technology, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu, Sabah, Malaysia.
authors.forename: P C
authors.initials: PC
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia.
authors.forename: H H
authors.initials: HH
authors.lastname: Lam
authors.affiliation: Department of Ophthalmology, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia.
authors.forename: S A
authors.initials: SA
authors.lastname: Ghani
authors.affiliation: Department of Ophthalmology, University of Malaya Medical Center, Kuala Lumpur, Malaysia.
authors.forename: V
authors.initials: V
authors.lastname: Subrayan
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia khchua@um.edu.my.
authors.forename: K H
authors.initials: KH
authors.lastname: Chua
mesh_terms: D015783:Aniridia / Q000235:genetics* / Q000473:pathology; D044466:Asian People / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D059014:High-Throughput Nucleotide Sequencing; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008296:Malaysia; D008297:Male; D009154:Mutation; D009691:Nucleic Acid Denaturation; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins