Purpose: To report a novel mutation of the ABCC6 gene in a Japanese family tha t had a case of pseudoxanthoma elasticum (PXE) another with PXE and retinitis pi gmentosa. Methods: Ophthalmologic examinations were perfo...Purpose: To report a novel mutation of the ABCC6 gene in a Japanese family tha t had a case of pseudoxanthoma elasticum (PXE) another with PXE and retinitis pi gmentosa. Methods: Ophthalmologic examinations were performed, and the ABCC6 gen e was analysed by direct genomic sequencing. Results: Fundus examinations of the 48-year-old proband disclosed angioid streaks and a peud’orange apparance of the retina of the both eyes, whereas both of his 25-and 20-year-old daughter s had pigmentary degeneration and angioid streaks. In the sibilings, the mixed cone-rod ERG was almost nond etectable, whereas that of the proband was well-preserved. Molecular genetic an alysis revealed that the proband has a homozygous nonsense mutation at the 595 b p in the ABCC6, and the siblings were heterozygous for the same mutation. This m utation was not detected in Japanese subjects in the JSNP database (http:// snp. ims.u-tokyo.ac.jp/). Conculsions: Our results demonstrated an association betwe en a novel mutation in the ABCC6 gene and PXE in a Japanese family.展开更多
Pseudogenes are frequently encountered noncoding sequences with a high sequence similarity to their protein-coding paralogue.For this reason,their presence is often considered troublesome in molecular diagnostics.In p...Pseudogenes are frequently encountered noncoding sequences with a high sequence similarity to their protein-coding paralogue.For this reason,their presence is often considered troublesome in molecular diagnostics.In pseudoxanthoma elasticum(PXE),a disease predominantly caused by mutations in ATPbinding cassette family C member 6(ABCC6),the presence of two pseudogenes complicates the analysis of sequence data.With whole-exome sequencing(WES)becoming the standard of care in molecular diagnostics,we wanted to evaluate whether this technique is as reliable as gene-specific targeted enrichment analysis for the analysis of ABCC6.We established a PCR-based targeted enrichment and next-generation sequencing testing approach and demonstrated that the ABCC6-specific enrichment combined with the applied mapping algorithm overcomes the complication of ABCC6 pseudogene aspecificities,contrary to WES.We propose a time-and cost-efficient diagnostic strategy for comprehensive and accurate molecular genetic testing of PXE,which is highly automatable.展开更多
文摘Purpose: To report a novel mutation of the ABCC6 gene in a Japanese family tha t had a case of pseudoxanthoma elasticum (PXE) another with PXE and retinitis pi gmentosa. Methods: Ophthalmologic examinations were performed, and the ABCC6 gen e was analysed by direct genomic sequencing. Results: Fundus examinations of the 48-year-old proband disclosed angioid streaks and a peud’orange apparance of the retina of the both eyes, whereas both of his 25-and 20-year-old daughter s had pigmentary degeneration and angioid streaks. In the sibilings, the mixed cone-rod ERG was almost nond etectable, whereas that of the proband was well-preserved. Molecular genetic an alysis revealed that the proband has a homozygous nonsense mutation at the 595 b p in the ABCC6, and the siblings were heterozygous for the same mutation. This m utation was not detected in Japanese subjects in the JSNP database (http:// snp. ims.u-tokyo.ac.jp/). Conculsions: Our results demonstrated an association betwe en a novel mutation in the ABCC6 gene and PXE in a Japanese family.
基金supported by a Methusalem grant(BOF08/01M01108)from Ghent Universityfunded by Ghent University+1 种基金FWOthe Flemish Government-department EWI。
文摘Pseudogenes are frequently encountered noncoding sequences with a high sequence similarity to their protein-coding paralogue.For this reason,their presence is often considered troublesome in molecular diagnostics.In pseudoxanthoma elasticum(PXE),a disease predominantly caused by mutations in ATPbinding cassette family C member 6(ABCC6),the presence of two pseudogenes complicates the analysis of sequence data.With whole-exome sequencing(WES)becoming the standard of care in molecular diagnostics,we wanted to evaluate whether this technique is as reliable as gene-specific targeted enrichment analysis for the analysis of ABCC6.We established a PCR-based targeted enrichment and next-generation sequencing testing approach and demonstrated that the ABCC6-specific enrichment combined with the applied mapping algorithm overcomes the complication of ABCC6 pseudogene aspecificities,contrary to WES.We propose a time-and cost-efficient diagnostic strategy for comprehensive and accurate molecular genetic testing of PXE,which is highly automatable.
