Genotype–phenotype correlation of PAX6 gene mutations in aniridia

被引：48
作者：
Tadashi Yokoi
Sachiko Nishina
Maki Fukami
Tsutomu Ogata
Katsuhiro Hosono
Yoshihiro Hotta
Noriyuki Azuma
机构：
[1] National Center for Child Health and Development,Department of Ophthalmology and Laboratory for Visual Science
[2] National Research Institute for Child Health and Development,Department of Molecular Endocrinology
[3] Hamamatsu University School of Medicine,Department of Ophthalmology
来源：
Human Genome Variation | / 3卷 / 1期
关键词：
D O I：
10.1038/hgv.2015.52
中图分类号：
学科分类号：
摘要：
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.
引用
收藏
相关论文
共 134 条
[11]  
Prosser J(2008)Genetic analysis of chromosome 11p13 and the PAX6 gene in a series of 125 cases referred with aniridia Am J Med Genetics A 146A 558-569
[12]  
Seawright A(1994)Human haploinsufficiency--one for sorrow, two for joy Nat Genet 7 5-7
[13]  
Gehring WJ(2003)Screening for PAX6 gene mutations is consistent with haploinsufficiency as the main mechanism leading to various ocular defects Eur J Hum Genet 11 163-169
[14]  
Halder G(1998)Missense mutations in the PAX6 gene in aniridia Invest Ophthalmol Vis Sci 39 2524-2528
[15]  
Callaerts P(1992)Criteria to detect minimal expressivity within families with autosomal dominant aniridia Am J Opthalmol 114 700-707
[16]  
Gehring WJ(1999)Missense mutation in the alternative splice region of the PAX6 gene in eye anomalies Am J Hum Genet 65 656-663
[17]  
Kioussi C(2012)Two novel mutations in the EYS gene are possible major causes of autosomal recessive retinitis pigmentosa in the Japanese population PLoS One 7 e31036-471
[18]  
O'Connell S(2005)PAX6 mutations: genotype-phenotype correlations BMC Genet 6 27-525
[19]  
St-Onge L(1994)PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects Nat Genet 7 463-110
[20]  
Treier M(1991)Mouse small eye results from mutations in a paired-like homeobox-containing gene Nature 354 522-2546
12345678910