dc.creator | Méndez-Vidal, Cristina | es |
dc.creator | Bravo-Gil, Nereida | es |
dc.creator | González del Pozo, María | es |
dc.creator | Vela-Boza, Alicia | es |
dc.creator | Dopazo, Joaquín | es |
dc.creator | Borrego, Salud | es |
dc.creator | Antiñolo Gil, Guillermo | es |
dc.date.accessioned | 2021-05-11T17:59:18Z | |
dc.date.available | 2021-05-11T17:59:18Z | |
dc.date.issued | 2014-12-14 | |
dc.identifier.citation | Méndez-Vidal, C., Bravo-Gil, N., González del Pozo, M., Vela-Boza, A., Dopazo, J., Borrego, S. y Antiñolo Gil, G. (2014). Novel RP1 mutations and a recurrent BBS1 variant explain the co-existence of two distinct retinal phenotypes in the same pedigree. BMC Genetics, 15 (1), art.n.143. | |
dc.identifier.issn | 1471-2156 | es |
dc.identifier.uri | https://hdl.handle.net/11441/108894 | |
dc.description.abstract | Background: Molecular diagnosis of Inherited Retinal Dystrophies (IRD) has long been challenging due to the
extensive clinical and genetic heterogeneity present in this group of disorders. Here, we describe the clinical
application of an integrated next-generation sequencing approach to determine the underlying genetic defects in
a Spanish family with a provisional clinical diagnosis of autosomal recessive Retinitis Pigmentosa (arRP).
Results: Exome sequencing of the index patient resulted in the identification of the homozygous BBS1 p.M390R
mutation. Sanger sequencing of additional members of the family showed lack of co-segregation of the p.M390R
variant in some individuals. Clinical reanalysis indicated co-ocurrence of two different phenotypes in the same family:
Bardet-Biedl syndrome in the individual harboring the BBS1 mutation and non-syndromic arRP in extended family
members. To identify possible causative mutations underlying arRP, we conducted disease-targeted gene sequencing
using a panel of 26 IRD genes. The in-house custom panel was validated using 18 DNA samples known to harbor
mutations in relevant genes. All variants were redetected, indicating a high mutation detection rate. This approach
allowed the identification of two novel heterozygous null mutations in RP1 (c.4582_4585delATCA; p.I1528Vfs*10 and
c.5962dupA; p.I1988Nfs*3) which co-segregated with the disease in arRP patients. Additionally, a mutational screening
in 96 patients of our cohort with genetically unresolved IRD revealed the presence of the c.5962dupA mutation in one
unrelated family.
Conclusions: The combination of molecular findings for RP1 and BBS1 genes through exome and gene panel
sequencing enabled us to explain the co-existence of two different retinal phenotypes in a family. The identification of
two novel variants in RP1 suggests that the use of panels containing the prevalent genes of a particular population,
together with an optimized data analysis pipeline, is an efficient and cost-effective approach that can be reliably
implemented into the routine diagnostic process of diverse inherited retinal disorders. Moreover, the identification of
these novel variants in two unrelated families supports the relatively high prevalence of RP1 mutations in Spanish
population and the role of private mutations for commonly mutated genes, while extending the mutational spectrum
of RP1 | es |
dc.description.sponsorship | Instituto de Salud Carlos III (ISCIII) | es |
dc.description.sponsorship | Spanish Ministry of Economy and Competitiveness, Spain (PI1102923, CIBERER ACCI and CDTI FEDER-Innterconecta EXP00052887/ITC-20111037) | es |
dc.description.sponsorship | Foundation Ramón Areces (CIVP16A1856) | es |
dc.description.sponsorship | ISCIII fellowship FI12/00545 | es |
dc.format | application/pdf | es |
dc.format.extent | 11 p. | es |
dc.language.iso | eng | es |
dc.publisher | BioMed Central Ltd. | es |
dc.relation.ispartof | BMC Genetics, 15 (1), art.n.143. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Bardet-Biedl syndrome | es |
dc.subject | BBS1 | es |
dc.subject | Inherited retinal dystrophies | es |
dc.subject | Next-generation sequencing | es |
dc.subject | Retinitis pigmentosa | es |
dc.subject | RP1 | es |
dc.title | Novel RP1 mutations and a recurrent BBS1 variant explain the co-existence of two distinct retinal phenotypes in the same pedigree | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Cirugía | es |
dc.relation.projectID | PI1102923 | es |
dc.relation.projectID | Innterconecta EXP00052887/ITC-20111037 | es |
dc.relation.projectID | CIVP16A1856 | es |
dc.relation.projectID | FI12/00545 | es |
dc.relation.publisherversion | https://bmcgenomdata.biomedcentral.com/articles/10.1186/s12863-014-0143-2 | es |
dc.identifier.doi | 10.1186/s12863-014-0143-2 | es |
dc.journaltitle | BMC Genetics | es |
dc.publication.volumen | 15 | es |
dc.publication.issue | 1 | es |
dc.publication.initialPage | art.n.143 | es |