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Large novel deletions detected in Chinese families with aniridia: correlation between genotype and phenotype.

Zhang X, Zhang Q, Tong Y, Dai H, Zhao X, Bai F, Xu L, Li Y - Mol. Vis. (2011)

Bottom Line: No mutation in PAX6 was identified after PCR-sequencing.Through MLPA analysis, a large deletion including the whole PAX6 gene, DKFZp686k1684 (hypothetical LOC440034), and the RCN1 (reticulocalbin 1) gene was detected in family 85; a 3' deletion to the PAX6 gene including the ELP4 (elongator complex protein 4) and the DCDC1 (doublecortin domain containing 1) gene was identified in family 86.The two large deletions were confirmed with linkage analysis and the "loss of heterozygous" in the different PAX6 regions were co-segregated with the phenotype of the two families, respectively.Patients with the PAX6 contiguous gene deletion, including the RCN1 gene, presented more severe vision impairments than those carrying the PAX6 3' deletion.

View Article: PubMed Central - PubMed

Affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China.

ABSTRACT

Purpose: To describe the clinical and genetic findings in two Chinese families with aniridia and other ocular abnormalities.

Methods: Two unrelated families were examined clinically. After informed consent was obtained, genomic DNA was extracted from the venous blood of all participants. Mutation screening of all exons of the PAX6 (paired box gene 6) gene was performed by direct sequencing of PCR-amplified DNA fragments. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect large deletions. Linkage analysis was used to validate the large deletions revealed by MLPA in all available family members.

Results: Clinical examination and pedigree analysis revealed one four-generation family (85) and one three- generation family (86) with total aniridia, congenital cataracts, foveal hypoplasia, and glaucoma. No mutation in PAX6 was identified after PCR-sequencing. Through MLPA analysis, a large deletion including the whole PAX6 gene, DKFZp686k1684 (hypothetical LOC440034), and the RCN1 (reticulocalbin 1) gene was detected in family 85; a 3' deletion to the PAX6 gene including the ELP4 (elongator complex protein 4) and the DCDC1 (doublecortin domain containing 1) gene was identified in family 86.The two large deletions were confirmed with linkage analysis and the "loss of heterozygous" in the different PAX6 regions were co-segregated with the phenotype of the two families, respectively.

Conclusions: Patients with the PAX6 contiguous gene deletion, including the RCN1 gene, presented more severe vision impairments than those carrying the PAX6 3' deletion. Large deletions may account for several Chinese families and sporadic cases with aniridia and screening for these kinds of alterations should be included in aniridia patients' analyses.

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Related in: MedlinePlus

Family structure and haplotype analysis of two Chinese families with aniridia. Pedigree and haplotype analysis of family 85 and 86 with aniridia showed “loss of heterozygous” segregation with the microsatellite marker PAX6.CA/GT (family 85), D11S995, and D11S2001 (family 86), respectively. All markers are on chromosome 11, listed in descending order from the centromeric end. Squares indicate males; circles indicate females; slashed symbols indicate deceased; solid symbols indicate affected; open symbols indicate unaffected.
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f2: Family structure and haplotype analysis of two Chinese families with aniridia. Pedigree and haplotype analysis of family 85 and 86 with aniridia showed “loss of heterozygous” segregation with the microsatellite marker PAX6.CA/GT (family 85), D11S995, and D11S2001 (family 86), respectively. All markers are on chromosome 11, listed in descending order from the centromeric end. Squares indicate males; circles indicate females; slashed symbols indicate deceased; solid symbols indicate affected; open symbols indicate unaffected.

Mentions: We have identified one four-generation family (#85) and one three- generation family (#86) with aniridia. The inheritance pattern in the families was autosomal dominant (Figure 2). After clinical examinations and a review of hospital records, 11 individuals in family 85 were found to have aniridia. All patients presented bilateral complete absence of iris, severe congenital nystagmus, and congenital cataracts (Figure 3A,C). Foveal hypoplasia was observed in all fourth-generation patients except (IV-6; Figure 3D). The ERG of patient IV-7 showed slight cone cell dysfunction. The proband (III-4), her father, and her brother presented high intraocular pressure (IOP) and late stage glaucoma changes in the optic disc (Figure 3B). Due to the progressive density of the lens opacification, the fovea of patients in the second and third- generation and patient IV-6 could not be observed clearly. In family 86, five patients were identified and all patients had bilateral complete absence of iris and congenital cataracts (Figure 3E,G). Neither mental retardation nor other general abnormalities was observed or documented in all patients from the two families. Their detailed clinical features are summarized in Table 3.


Large novel deletions detected in Chinese families with aniridia: correlation between genotype and phenotype.

Zhang X, Zhang Q, Tong Y, Dai H, Zhao X, Bai F, Xu L, Li Y - Mol. Vis. (2011)

Family structure and haplotype analysis of two Chinese families with aniridia. Pedigree and haplotype analysis of family 85 and 86 with aniridia showed “loss of heterozygous” segregation with the microsatellite marker PAX6.CA/GT (family 85), D11S995, and D11S2001 (family 86), respectively. All markers are on chromosome 11, listed in descending order from the centromeric end. Squares indicate males; circles indicate females; slashed symbols indicate deceased; solid symbols indicate affected; open symbols indicate unaffected.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3044699&req=5

f2: Family structure and haplotype analysis of two Chinese families with aniridia. Pedigree and haplotype analysis of family 85 and 86 with aniridia showed “loss of heterozygous” segregation with the microsatellite marker PAX6.CA/GT (family 85), D11S995, and D11S2001 (family 86), respectively. All markers are on chromosome 11, listed in descending order from the centromeric end. Squares indicate males; circles indicate females; slashed symbols indicate deceased; solid symbols indicate affected; open symbols indicate unaffected.
Mentions: We have identified one four-generation family (#85) and one three- generation family (#86) with aniridia. The inheritance pattern in the families was autosomal dominant (Figure 2). After clinical examinations and a review of hospital records, 11 individuals in family 85 were found to have aniridia. All patients presented bilateral complete absence of iris, severe congenital nystagmus, and congenital cataracts (Figure 3A,C). Foveal hypoplasia was observed in all fourth-generation patients except (IV-6; Figure 3D). The ERG of patient IV-7 showed slight cone cell dysfunction. The proband (III-4), her father, and her brother presented high intraocular pressure (IOP) and late stage glaucoma changes in the optic disc (Figure 3B). Due to the progressive density of the lens opacification, the fovea of patients in the second and third- generation and patient IV-6 could not be observed clearly. In family 86, five patients were identified and all patients had bilateral complete absence of iris and congenital cataracts (Figure 3E,G). Neither mental retardation nor other general abnormalities was observed or documented in all patients from the two families. Their detailed clinical features are summarized in Table 3.

Bottom Line: No mutation in PAX6 was identified after PCR-sequencing.Through MLPA analysis, a large deletion including the whole PAX6 gene, DKFZp686k1684 (hypothetical LOC440034), and the RCN1 (reticulocalbin 1) gene was detected in family 85; a 3' deletion to the PAX6 gene including the ELP4 (elongator complex protein 4) and the DCDC1 (doublecortin domain containing 1) gene was identified in family 86.The two large deletions were confirmed with linkage analysis and the "loss of heterozygous" in the different PAX6 regions were co-segregated with the phenotype of the two families, respectively.Patients with the PAX6 contiguous gene deletion, including the RCN1 gene, presented more severe vision impairments than those carrying the PAX6 3' deletion.

View Article: PubMed Central - PubMed

Affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China.

ABSTRACT

Purpose: To describe the clinical and genetic findings in two Chinese families with aniridia and other ocular abnormalities.

Methods: Two unrelated families were examined clinically. After informed consent was obtained, genomic DNA was extracted from the venous blood of all participants. Mutation screening of all exons of the PAX6 (paired box gene 6) gene was performed by direct sequencing of PCR-amplified DNA fragments. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect large deletions. Linkage analysis was used to validate the large deletions revealed by MLPA in all available family members.

Results: Clinical examination and pedigree analysis revealed one four-generation family (85) and one three- generation family (86) with total aniridia, congenital cataracts, foveal hypoplasia, and glaucoma. No mutation in PAX6 was identified after PCR-sequencing. Through MLPA analysis, a large deletion including the whole PAX6 gene, DKFZp686k1684 (hypothetical LOC440034), and the RCN1 (reticulocalbin 1) gene was detected in family 85; a 3' deletion to the PAX6 gene including the ELP4 (elongator complex protein 4) and the DCDC1 (doublecortin domain containing 1) gene was identified in family 86.The two large deletions were confirmed with linkage analysis and the "loss of heterozygous" in the different PAX6 regions were co-segregated with the phenotype of the two families, respectively.

Conclusions: Patients with the PAX6 contiguous gene deletion, including the RCN1 gene, presented more severe vision impairments than those carrying the PAX6 3' deletion. Large deletions may account for several Chinese families and sporadic cases with aniridia and screening for these kinds of alterations should be included in aniridia patients' analyses.

Show MeSH
Related in: MedlinePlus