Varios genes descartados como causantes de retinosis pigmentaria autosómica recesiva en dos familias costarricenses
Fecha
1998-07
Tipo
artículo original
Autores
Leal Esquivel, Alejandro
Gutiérrez Espeleta, Gustavo A.
Barrantes Mesén, Ramiro
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Resumen
Se estudiaron dos familias costarricenses con Retinosis Pigmentaria (RP) de herencia autosomica recesiva, con el fin de descartar genes relacionados con la enfermedad. Para esto se efectuó un análisis de ligamiento con marcadores polimórficos por repeticiones en tandem (STRPs). En una familia (C1) Ios afectados presentan una degeneración de aparición temprana y severe. En Ia otra familia (P1) la aparición es temprana pero con una degeneración mas lenta que en C1. Las diferencias fenotipicas sugieren que se trate de mutaciones diferentes en ambas familias. En Cl los siguientes genes quedan descartados (Z (0,0) = ) : el de herencia autosomica recesiva (RPAR) de la región 1q31-32.1, R PAR por mutación en la fosfodiesterasa B en 4p16.3, RPAR de 6p a 20 cM del gen de la periferina, el de Ia distrofia macular del cromosoma 6, y del protooncogen myc. Por Su parte, el puntaje Lod con el marcador RDS no permite descartar con certeza al gen RDS (Z (0,0) = — 0,0083) y se observan puntajes Lod positivos en el caso de los marcadores mycen 8q24.12-q24.13 (Z (0,2) = 0,3050) y periferina/RDS en 6p12 (Z (0,1) = 0,2063), pero no son significativos. En P1 se descarta el gen que codifica la rodopsina, el de la fosfodesterasa S, el de RPAR cercano ale periferina, el de la periferina, RPAD del cromosoma 7 y el proto-oncogen myc. Por otra parte, se encontraron valores positivos en marcadores cercanos al gen de la rodopsina (RHO, Z (0.1). 0.3991), periferina (ADS, Z (0.2) =0.3390) y Usher 1A del cromosoma 14q (P1, Z (0,09) = 0.7647). En lo sucesivo deberán descartarse por complete las regiones correspondientes a genes que participan en la transmisión de la serial visual o que forman parte de alguna estructura en is retina. La metodología aquí seguida es Citil y factible en Costa Rica pare descartar genes implicados en enfermedades hereditarias humanas, y se puede utilizar pare conocer los orígenes de otras patologías, realizar un diagnostico preciso, ofrecer asesorfa genética y apoyar el diseño de terapias
In order to discard some candidate genes for autosomal recessive Retinitis Pigmentosa (RP), two families with this disease were studied. Linkage analysis was done, using polymorphic markers (STRPs). In one family (C1) affected members present an early onset and severe degeneration of the retina. In the other family (P1) the onset is earlier but the degeneration is slower than in Cl. Phenotypic differences indicate that there are different mutations in both families. The following genes are not responsible for the disease in family Cl (Z autosomal recessive RP (arRP) on 1q31 32.1, arRP by mutation in the PDEB gene on4p16.3, arRP on 6p at 20 cM of peripherin gene, macular dystrophy on chromosome 6 and proto-oncogene myc. On the other hand, the marker ADS' lod score certainly does not allow discard in a the peripherin gene as responsible (Z(0.1)= - 0.0083), and there are positive lod scores for myc on 8q (Z (0.2)= 0.3050) and peripherin/RDS on 6p12 (Z(0.1)= 0,2063), but they are not significant. In the case of P1, results suggest that the following genes could be discarded: rodopsin, PDEB, arRP close to peripherhin, peripherin/RDS, adRP on chromosome 7 and myc. Nevertheless positive values were found near regions of rodopsin (RHO, Z(0.1)= 0.3991), peripherin (RDS, Z(0.2)= 0.3390) and Usher 1A on 14q (P1, Z(0,09)= 0.7647). The next step is to discard the regions with genes implicated in the visual transmission system or in the structure of the retina. This methodology can be used in Costa Rica for discarding genes implicated in other human hereditary diseases, for ascertaining information on the origen of certain pathologies, in order to get a precise diagnosis, to offer genetic counseling, and to support the design of therapies.
In order to discard some candidate genes for autosomal recessive Retinitis Pigmentosa (RP), two families with this disease were studied. Linkage analysis was done, using polymorphic markers (STRPs). In one family (C1) affected members present an early onset and severe degeneration of the retina. In the other family (P1) the onset is earlier but the degeneration is slower than in Cl. Phenotypic differences indicate that there are different mutations in both families. The following genes are not responsible for the disease in family Cl (Z autosomal recessive RP (arRP) on 1q31 32.1, arRP by mutation in the PDEB gene on4p16.3, arRP on 6p at 20 cM of peripherin gene, macular dystrophy on chromosome 6 and proto-oncogene myc. On the other hand, the marker ADS' lod score certainly does not allow discard in a the peripherin gene as responsible (Z(0.1)= - 0.0083), and there are positive lod scores for myc on 8q (Z (0.2)= 0.3050) and peripherin/RDS on 6p12 (Z(0.1)= 0,2063), but they are not significant. In the case of P1, results suggest that the following genes could be discarded: rodopsin, PDEB, arRP close to peripherhin, peripherin/RDS, adRP on chromosome 7 and myc. Nevertheless positive values were found near regions of rodopsin (RHO, Z(0.1)= 0.3991), peripherin (RDS, Z(0.2)= 0.3390) and Usher 1A on 14q (P1, Z(0,09)= 0.7647). The next step is to discard the regions with genes implicated in the visual transmission system or in the structure of the retina. This methodology can be used in Costa Rica for discarding genes implicated in other human hereditary diseases, for ascertaining information on the origen of certain pathologies, in order to get a precise diagnosis, to offer genetic counseling, and to support the design of therapies.
Descripción
Artículo científico -- Universidad de Costa Rica, Instituto de Investigaciones en Salud. 1998
Palabras clave
diagnóstico molecular, retinosis pigmentaria, marcadores polimórficos, Genética humana, Enfermedad genética