Evento
Whole Exome Sequencing analysis of constitutional DNA in argentinean Retinoblastoma patients
Parma, Diana Lidia; Luce, Leonela Natalia
; Carcione, María Micaela
; Mazzanti, Chiara; Ferrer, Marcela Maria
; Giliberto, Florencia
; Szijan, Irena
Tipo del evento:
Reunión
Nombre del evento:
LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Fecha del evento:
13/11/2019
Institución Organizadora:
Sociedad Argentina de Investigación Clínica;
Asociación Argentina de Farmacología Experimental;
Sociedad Argentina de Biología;
Sociedad Argentina de Protozoología;
Asociación Argentina de Nanomedicinas;
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio;
The Histochemical Society;
Título de la revista:
Medicina (Buenos Aires)
Editorial:
Fundación Revista Medicina
ISSN:
0025-7680
Idioma:
Inglés
Clasificación temática:
Resumen
Whole Exome Sequencing analysis of constitutional DNA in argentinean Retinoblastoma patientsParma, Diana; Luce, Leonela; Carcione Micaela; Mazzanti Chiara; Ferrer, Marcela; Giliberto Florencia; Szijan Irena.Retinoblastoma (RB) is a pediatric tumor of the developing retina, caused by mutations in RB1 tumor suppressor gene. RB1 molecular alterations are small mutations in 80% of cases and gross deletions/duplications in 20%. In hereditary RB, identification of mutations is essential for genetic assessment. The purpose of this work was to detect small mutations in RB1 by Whole Exome Sequencing (WES) in 7 argentinean RB patients. WES was performed in leukocytes DNA from 2 familial and 1 sporadic bilateral and 4 early unilateral RB cases. The pathogenicity of the identified variants was determined according to: its presence in RB1 mutation database; its absence in sequence consortiums (ExAC and GnomAD); and predictive softwares. All pathogenic mutations were corroborated by Sanger Sequencing. Gross mutations were screened by MLPA. We have found an average of 13 sequence variants in RB1, 5 of them were present in all patients. We identified the disease causing mutations in 2/7 cases. In one bilateral familial case, a nonsense mutation (g.70286C>A) in exon 12 was detected, the patient´s affected father showed the same mutation. The sporadic bilateral RB presented a substitution (g.5550G>A) in the last nucleotide of exon 2, according to previous reports this variant leads to aberrant splicing. In an unilateral RB patient, a likely benign inframe deletion was observed. The 4 unilateral and the other familial bilateral RB patients did not show pathogenic small mutations nor gross molecular alterations in RB1. Thus, screening was enlarged to genes associated with RB1 pathways and other tumors, but no deleterious variant was identified. We can conclude that WES was able to find constitutional mutations in RB1 gene, allowing confirmation of diagnosis and genetic assessment. Further studies must be performed in patients with no causative mutation found. Finally, the importance of this work relies on the fact that is the first one applying WES for RB molecular diagnosis in Argentina.
Palabras clave:
EXOME
,
SEQUENCING
,
RETINOBLASTOMA
,
PATIENTS
Archivos asociados
Licencia
Identificadores
Colecciones
Eventos(INIGEM)
Eventos de INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Eventos de INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Citación
Whole Exome Sequencing analysis of constitutional DNA in argentinean Retinoblastoma patients; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 200-200
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