Exome sequencing reveals novel and recurrent mutations with clinical significance in inherited retinal dystrophies.
This study aimed to identify the underlying molecular genetic cause in four Spanish families clinically diagnosed of Retinitis Pigmentosa (RP), comprising one autosomal dominant RP (adRP), two autosomal recessive RP (arRP) and one with two possible modes of inheritance: arRP or X-Linked RP (XLRP). W...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4278866?pdf=render |
| _version_ | 1824009739491606528 |
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| author | María González-del Pozo Cristina Méndez-Vidal Nereida Bravo-Gil Alicia Vela-Boza Joaquin Dopazo Salud Borrego Guillermo Antiñolo |
| author_facet | María González-del Pozo Cristina Méndez-Vidal Nereida Bravo-Gil Alicia Vela-Boza Joaquin Dopazo Salud Borrego Guillermo Antiñolo |
| author_sort | María González-del Pozo |
| collection | DOAJ |
| description | This study aimed to identify the underlying molecular genetic cause in four Spanish families clinically diagnosed of Retinitis Pigmentosa (RP), comprising one autosomal dominant RP (adRP), two autosomal recessive RP (arRP) and one with two possible modes of inheritance: arRP or X-Linked RP (XLRP). We performed whole exome sequencing (WES) using NimbleGen SeqCap EZ Exome V3 sample preparation kit and SOLID 5500xl platform. All variants passing filter criteria were validated by Sanger sequencing to confirm familial segregation and the absence in local control population. This strategy allowed the detection of: (i) one novel heterozygous splice-site deletion in RHO, c.937-2_944del, (ii) one rare homozygous mutation in C2orf71, c.1795T>C; p.Cys599Arg, not previously associated with the disease, (iii) two heterozygous null mutations in ABCA4, c.2041C>T; p.R681* and c.6088C>T; p.R2030*, and (iv) one mutation, c.2405-2406delAG; p.Glu802Glyfs*31 in the ORF15 of RPGR. The molecular findings for RHO and C2orf71 confirmed the initial diagnosis of adRP and arRP, respectively, while patients with the two ABCA4 mutations, both previously associated with Stargardt disease, presented symptoms of RP with early macular involvement. Finally, the X-Linked inheritance was confirmed for the family with the RPGR mutation. This latter finding allowed the inclusion of carrier sisters in our preimplantational genetic diagnosis program. |
| first_indexed | 2024-12-18T21:14:38Z |
| format | Article |
| id | doaj.art-326e78cc72d54add9da2f2bb15cfb5cf |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-18T21:14:38Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-326e78cc72d54add9da2f2bb15cfb5cf2022-12-21T20:52:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11617610.1371/journal.pone.0116176Exome sequencing reveals novel and recurrent mutations with clinical significance in inherited retinal dystrophies.María González-del PozoCristina Méndez-VidalNereida Bravo-GilAlicia Vela-BozaJoaquin DopazoSalud BorregoGuillermo AntiñoloThis study aimed to identify the underlying molecular genetic cause in four Spanish families clinically diagnosed of Retinitis Pigmentosa (RP), comprising one autosomal dominant RP (adRP), two autosomal recessive RP (arRP) and one with two possible modes of inheritance: arRP or X-Linked RP (XLRP). We performed whole exome sequencing (WES) using NimbleGen SeqCap EZ Exome V3 sample preparation kit and SOLID 5500xl platform. All variants passing filter criteria were validated by Sanger sequencing to confirm familial segregation and the absence in local control population. This strategy allowed the detection of: (i) one novel heterozygous splice-site deletion in RHO, c.937-2_944del, (ii) one rare homozygous mutation in C2orf71, c.1795T>C; p.Cys599Arg, not previously associated with the disease, (iii) two heterozygous null mutations in ABCA4, c.2041C>T; p.R681* and c.6088C>T; p.R2030*, and (iv) one mutation, c.2405-2406delAG; p.Glu802Glyfs*31 in the ORF15 of RPGR. The molecular findings for RHO and C2orf71 confirmed the initial diagnosis of adRP and arRP, respectively, while patients with the two ABCA4 mutations, both previously associated with Stargardt disease, presented symptoms of RP with early macular involvement. Finally, the X-Linked inheritance was confirmed for the family with the RPGR mutation. This latter finding allowed the inclusion of carrier sisters in our preimplantational genetic diagnosis program.http://europepmc.org/articles/PMC4278866?pdf=render |
| spellingShingle | María González-del Pozo Cristina Méndez-Vidal Nereida Bravo-Gil Alicia Vela-Boza Joaquin Dopazo Salud Borrego Guillermo Antiñolo Exome sequencing reveals novel and recurrent mutations with clinical significance in inherited retinal dystrophies. PLoS ONE |
| title | Exome sequencing reveals novel and recurrent mutations with clinical significance in inherited retinal dystrophies. |
| title_full | Exome sequencing reveals novel and recurrent mutations with clinical significance in inherited retinal dystrophies. |
| title_fullStr | Exome sequencing reveals novel and recurrent mutations with clinical significance in inherited retinal dystrophies. |
| title_full_unstemmed | Exome sequencing reveals novel and recurrent mutations with clinical significance in inherited retinal dystrophies. |
| title_short | Exome sequencing reveals novel and recurrent mutations with clinical significance in inherited retinal dystrophies. |
| title_sort | exome sequencing reveals novel and recurrent mutations with clinical significance in inherited retinal dystrophies |
| url | http://europepmc.org/articles/PMC4278866?pdf=render |
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