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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

Anterior segment of proband (IV:2) and the proband’s mother (III:5). A and B show iris anomalies, and nasally and superiorly displaced pupil and cataract in both eyes of proband (IV:2). C and D show mild nasally displaced pupil and cataract of the proband’s mother (III:5).
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f2: Anterior segment of proband (IV:2) and the proband’s mother (III:5). A and B show iris anomalies, and nasally and superiorly displaced pupil and cataract in both eyes of proband (IV:2). C and D show mild nasally displaced pupil and cataract of the proband’s mother (III:5).

Mentions: The proband (patient IV:2, a seven-year-old boy, Figure 1) presented with nystagmus, cataract, and iris anomalies (corectopia and coloboma of iris). In addition, this patient also presented with mental retardation and muscle spasms. His corrected visual acuity was 0.1 OD and 0.1 OS. Intraocular pressure (IOP) was 17 mmHg in the right eye and 16.8 mmHg in the left eye. He was noted to have nystagmus after birth. Clinically, he showed rapid jerk nystagmus with poorly developed fixation ability (Figure 2A,B). B-scanning revealed abnormally short axial lengths and deep anterior chambers (data not shown). Fundus details could not be seen, but retinas were attached per ultrasound.


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)

Anterior segment of proband (IV:2) and the proband’s mother (III:5). A and B show iris anomalies, and nasally and superiorly displaced pupil and cataract in both eyes of proband (IV:2). C and D show mild nasally displaced pupil and cataract of the proband’s mother (III:5).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Anterior segment of proband (IV:2) and the proband’s mother (III:5). A and B show iris anomalies, and nasally and superiorly displaced pupil and cataract in both eyes of proband (IV:2). C and D show mild nasally displaced pupil and cataract of the proband’s mother (III:5).
Mentions: The proband (patient IV:2, a seven-year-old boy, Figure 1) presented with nystagmus, cataract, and iris anomalies (corectopia and coloboma of iris). In addition, this patient also presented with mental retardation and muscle spasms. His corrected visual acuity was 0.1 OD and 0.1 OS. Intraocular pressure (IOP) was 17 mmHg in the right eye and 16.8 mmHg in the left eye. He was noted to have nystagmus after birth. Clinically, he showed rapid jerk nystagmus with poorly developed fixation ability (Figure 2A,B). B-scanning revealed abnormally short axial lengths and deep anterior chambers (data not shown). Fundus details could not be seen, but retinas were attached per ultrasound.

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