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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

The normalized MLPA results of the probands of the two families. A: The normalized MLPA result of III-4 of family 85. B: The result of II-4 of family 86. The height of the columns represents of the dosage of the respective segments in the genomic DNA with two alleles. The light blue columns represent chromosome 11p13 specific probes. The orange columns represent the deleted probes. The dark blue columns represent the control probes. The allele dosage of the deleted probes was found in the range of about 0.5–0.7 of normal control, which corresponds to one allele.
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f4: The normalized MLPA results of the probands of the two families. A: The normalized MLPA result of III-4 of family 85. B: The result of II-4 of family 86. The height of the columns represents of the dosage of the respective segments in the genomic DNA with two alleles. The light blue columns represent chromosome 11p13 specific probes. The orange columns represent the deleted probes. The dark blue columns represent the control probes. The allele dosage of the deleted probes was found in the range of about 0.5–0.7 of normal control, which corresponds to one allele.

Mentions: Using the MLPA Kits P219, two different deletions were detected in the two families (Figure 4). In family 85, a deletion of the whole PAX6 gene, the DKFZ p686k1684 gene, and the RCN1 gene was found; in family 86, a deletion of the ELP4 gene and the DCDC1 gene, which is located in the 3′ region of the PAX6 gene, was identified.


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)

The normalized MLPA results of the probands of the two families. A: The normalized MLPA result of III-4 of family 85. B: The result of II-4 of family 86. The height of the columns represents of the dosage of the respective segments in the genomic DNA with two alleles. The light blue columns represent chromosome 11p13 specific probes. The orange columns represent the deleted probes. The dark blue columns represent the control probes. The allele dosage of the deleted probes was found in the range of about 0.5–0.7 of normal control, which corresponds to one allele.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: The normalized MLPA results of the probands of the two families. A: The normalized MLPA result of III-4 of family 85. B: The result of II-4 of family 86. The height of the columns represents of the dosage of the respective segments in the genomic DNA with two alleles. The light blue columns represent chromosome 11p13 specific probes. The orange columns represent the deleted probes. The dark blue columns represent the control probes. The allele dosage of the deleted probes was found in the range of about 0.5–0.7 of normal control, which corresponds to one allele.
Mentions: Using the MLPA Kits P219, two different deletions were detected in the two families (Figure 4). In family 85, a deletion of the whole PAX6 gene, the DKFZ p686k1684 gene, and the RCN1 gene was found; in family 86, a deletion of the ELP4 gene and the DCDC1 gene, which is located in the 3′ region of the PAX6 gene, was identified.

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