Xinghua Huang1, Yun Liu2, Xiurong Yu1, Qiuxiang Huang2, Chunli Lin2, Jian Zeng1, Fenghua Lan1, Zhihong Wang3. 1. Research Center for Molecular Diagnosis of Genetic Diseases, Fuzhou General Hospital, Clinical College of Fujian Medical University/Dongfang Hospital, Xiamen University Medical College, 156 Xi'erhuanbei Road, Fuzhou City, 350025, Fujian Province, People's Republic of China. 2. Department of Obstetrics & Gynecology, Center of Reproductive Medicine, Fuzhou General Hospital, Clinical College of Fujian Medical University/Dongfang Hospital, Xiamen University Medical College, Fuzhou, 350025, Fujian, China. 3. Research Center for Molecular Diagnosis of Genetic Diseases, Fuzhou General Hospital, Clinical College of Fujian Medical University/Dongfang Hospital, Xiamen University Medical College, 156 Xi'erhuanbei Road, Fuzhou City, 350025, Fujian Province, People's Republic of China. xmzhwang@xmu.edu.cn.
Abstract
OBJECTIVE: To investigate the usefulness of preimplantation genetic diagnosis (PGD) based on mutated allele revealed by sequencing with aneuploidy and linkage analyses (MARSALA) for a pedigree with X-linked retinitis pigmentosa (XLRP). METHODS: One pathogenic mutation (c.494G > A) of the retinitis pigmentosa GTPase regulator (RPGR) gene was identified in a pedigree affected by XLRP. Then, PGD was carried out for the couple, of which the wife was an XLRP carrier. Three blastocysts were biopsied and then MARSALA was performed by next-generation sequencing (NGS). Prenatal diagnosis was also carried out to confirm the PGD results. RESULTS: Three blastocysts were all unaffected. Then, one of the embryos was chosen randomly to be transferred, and the pregnancy was acquired successfully. The results of prenatal diagnosis were consistent with the PGD results. The fetus did not carry RPGR mutation (c.494G > A) and had normal chromosome karyotype. As a result, a healthy baby free of XLRP condition was born. CONCLUSION: The PGD method based on MARSALA was established and applied to a family with XLRP successfully. MARSALA will be a valid tool, not only for XLRP families but also for families affected with other monogenetic disorders, to prevent transmission of the genetic disease from parents to offspring.
OBJECTIVE: To investigate the usefulness of preimplantation genetic diagnosis (PGD) based on mutated allele revealed by sequencing with aneuploidy and linkage analyses (MARSALA) for a pedigree with X-linked retinitis pigmentosa (XLRP). METHODS: One pathogenic mutation (c.494G > A) of the retinitis pigmentosa GTPase regulator (RPGR) gene was identified in a pedigree affected by XLRP. Then, PGD was carried out for the couple, of which the wife was an XLRP carrier. Three blastocysts were biopsied and then MARSALA was performed by next-generation sequencing (NGS). Prenatal diagnosis was also carried out to confirm the PGD results. RESULTS: Three blastocysts were all unaffected. Then, one of the embryos was chosen randomly to be transferred, and the pregnancy was acquired successfully. The results of prenatal diagnosis were consistent with the PGD results. The fetus did not carry RPGR mutation (c.494G > A) and had normal chromosome karyotype. As a result, a healthy baby free of XLRP condition was born. CONCLUSION: The PGD method based on MARSALA was established and applied to a family with XLRP successfully. MARSALA will be a valid tool, not only for XLRP families but also for families affected with other monogenetic disorders, to prevent transmission of the genetic disease from parents to offspring.
Authors: G Altarescu; D A Zeevi; S Zeligson; S Perlberg; T Eldar-Geva; E J Margalioth; E Levy-Lahad; P Renbaum Journal: J Assist Reprod Genet Date: 2013-07-06 Impact factor: 3.412
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