title: Genotype-phenotype correlation of PAX6 gene mutations in aniridia.
abstract: The objective of this study was to investigate the genotype-phenotype correlation of the PAX6 gene in aniridia. We clinically examined 5 families and 16 sporadic patients with aniridia. We performed chromosomal analysis and PCR analysis of the PAX6 gene using patient genomic DNA. Chromosomal analysis demonstrated deletions at 11p13 in one allele in four sporadic patients. Seven nonsense mutations, two frameshifts (two insertions), four splice junction errors and two missense mutations were found, and all were heterozygous. The iris phenotype ranged from total to normal in each patient, and the characteristic phenotypes, including cataract, glaucoma or optic nerve hypoplasia, varied widely even among members of the same family. Foveal hypoplasia was detected in all patients except for one. No obvious genotype-phenotype correlation was identified; however, the aniridia phenotype between the two eyes in each patient was quite similar in all patients. Because PAX6 regulates numerous downstream genes and its expression is regulated by several factors during eye development, the aniridia phenotype may be complex even in family members. However, because PAX6 regulation, resulting from both paternal and maternal alleles associated with PAX6, is considered to be roughly similar in both eyes of each patient, the aniridia phenotype may be similar in both eyes of each patient.
authors.affiliation: Department of Ophthalmology and Laboratory for Visual Science, National Center for Child Health and Development , Tokyo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yokoi
authors.affiliation: Department of Ophthalmology and Laboratory for Visual Science, National Center for Child Health and Development , Tokyo, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Nishina
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development , Tokyo, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Fukami
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development , Tokyo, Japan.
authors.forename: Tsutomu
authors.identifier: 0000-0001-7178-9991
authors.initials: T
authors.lastname: Ogata
authors.affiliation: Department of Ophthalmology, Hamamatsu University School of Medicine , Hamamatsu, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hosono
authors.affiliation: Department of Ophthalmology, Hamamatsu University School of Medicine , Hamamatsu, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hotta
authors.affiliation: Department of Ophthalmology and Laboratory for Visual Science, National Center for Child Health and Development , Tokyo, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Azuma