Molecular genetics of familial nystagmus complicated with cataract and iris anomalies.
OBJECTIVE
Familial nystagmus complicated with cataract and iris anomalies are genetically heterogeneous, and the pathophysiological mechanisms remain unclear. It is anticipated that mutations in the paired box 6 (PAX6) gene play a major role in pathogenesis of malformations in anterior segment of the eye. In this study, we analyzed PAX6 in a Chinese pedigree of nystagmus, cataract and iris anomalies. This study will provide insights into the genetic basis of this disease.


METHODS
Complete ophthalmologic examinations were performed on four patients (excluding one dead patient) and four unaffected individuals in this four-generation family. All coding exons of PAX6 were amplified by polymerase chain reaction (PCR), sequenced and compared with reference database. The variations detected were evaluated in available family members as well as 110 normal controls. Possible changes in structure and function of the protein induced by amino acid variance were predicted by bioinformatics analysis.


RESULTS
Nystagmus, cataract or iris anomalies were found in all patients of this family, but the severity was different among these patients. A novel missense mutation in PAX6 was identified in all affected individuals but not in asymptomatic members and 110 normal controls. This mutation causes an amino acid substitution of proline to glutamine at position 118 (p.P118Q) of the paired domain of the PAX6 protein. Such a change may cause structural and functional changes of the protein based on bioinformatics analysis.


CONCLUSIONS
This study added a novel mutation to the existing spectrum of PAX6 mutations, suggesting that a mutation in PAX6 correlated with anterior segment disorders observed in this family.
Ophthalmic Laboratories & Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, PR China.
Naihong
N
Yan
Yongwang
Y
Zhao
Yun
Y
Wang
Airui
A
Xie
Haitao
H
Huang
Wenhan
W
Yu
Xuyang
X
Liu
Su-ping
SP
Cai
D000328:Adult; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D015783:Aniridia / Q000150:complications / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002386:Cataract / Q000150:complications / Q000235:genetics*; D002648:Child; D019295:Computational Biology; D004252:DNA Mutational Analysis; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D020417:Nystagmus, Congenital / Q000150:complications / Q000235:genetics*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010375:Pedigree; D012097:Repressor Proteins / Q000235:genetics*; D012720:Severity of Illness Index
D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins