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Molecular genetics of familial nystagmus complicated with cataract and iris anomalies.

Yan N, Zhao Y, Wang Y, Xie A, Huang H, Yu W, Liu X, Cai SP - Mol. Vis. (2011)

Bottom Line: All coding exons of PAX6 were amplified by polymerase chain reaction (PCR), sequenced and compared with reference database.Such a change may cause structural and functional changes of the protein based on bioinformatics analysis.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.

View Article: PubMed Central - PubMed

Affiliation: Ophthalmic Laboratories & Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, PR China.

ABSTRACT

Purpose: 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.

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Related in: MedlinePlus

Sequencing results of the PAX6 gene. A: a heterozygous C to A transversion at codon 118 in one patient from the family (arrowhead). B: Wild type sequence from an unaffected member.
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f3: Sequencing results of the PAX6 gene. A: a heterozygous C to A transversion at codon 118 in one patient from the family (arrowhead). B: Wild type sequence from an unaffected member.

Mentions: A novel heterozygous mutation, c.353 C>A, at codon 118 (CCA to CAA) of exon 6 in PAX6 was identified. This heterozygous mutation was present in all affected individuals whereas none of the unaffected family members and 110 normal control subjects examined carried the mutation (Figure 3). The affected individuals were heterozygous alleles with mutant and wild-type alleles. The unaffected members carried wild-type alleles.


Molecular genetics of familial nystagmus complicated with cataract and iris anomalies.

Yan N, Zhao Y, Wang Y, Xie A, Huang H, Yu W, Liu X, Cai SP - Mol. Vis. (2011)

Sequencing results of the PAX6 gene. A: a heterozygous C to A transversion at codon 118 in one patient from the family (arrowhead). B: Wild type sequence from an unaffected member.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198497&req=5

f3: Sequencing results of the PAX6 gene. A: a heterozygous C to A transversion at codon 118 in one patient from the family (arrowhead). B: Wild type sequence from an unaffected member.
Mentions: A novel heterozygous mutation, c.353 C>A, at codon 118 (CCA to CAA) of exon 6 in PAX6 was identified. This heterozygous mutation was present in all affected individuals whereas none of the unaffected family members and 110 normal control subjects examined carried the mutation (Figure 3). The affected individuals were heterozygous alleles with mutant and wild-type alleles. The unaffected members carried wild-type alleles.

Bottom Line: All coding exons of PAX6 were amplified by polymerase chain reaction (PCR), sequenced and compared with reference database.Such a change may cause structural and functional changes of the protein based on bioinformatics analysis.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.

View Article: PubMed Central - PubMed

Affiliation: Ophthalmic Laboratories & Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, PR China.

ABSTRACT

Purpose: 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.

Show MeSH
Related in: MedlinePlus