RESUMEN
To investigate the genetic etiology of anophthalmia and microphthalmia, we used exome sequencing in a Caucasian female with unilateral microphthalmia and coloboma, bilateral optic nerve hypoplasia, ventricular and atrial septal defects, and growth delays. We found two sequence variants in SALL4 - c.[575C>A], predicting p.(Ala192Glu), that was paternally inherited, and c.[2053G>C], predicting p.(Asp685His), that was maternally inherited. Haploinsufficiency for SALL4 due to nonsense or frameshift mutations has been associated with acro-renal ocular syndrome that is characterized by eye defects including Duane anomaly and coloboma, in addition to radial ray malformations and renal abnormalities. Our report is the first description of structural eye defects associated with two missense variants in SALL4 inherited in trans; the absence of reported findings in both parents suggests that both sequence variants are hypomorphic mutations and that both are needed for the ocular phenotype. SALL4 is expressed in the developing lens and regulates BMP4, leading us to speculate that altered BMP4 expression was responsible for the eye defects, but we could not demonstrate altered BMP4 expression in vitro after using small interfering RNAs (siRNAs) to reduce SALL4 expression. We conclude that SALL4 hypomorphic variants may influence eye development.
Asunto(s)
Coloboma/genética , Microftalmía/genética , Mutación Missense , Enfermedades del Nervio Óptico/congénito , Factores de Transcripción/genética , Exoma/genética , Femenino , Trastornos del Crecimiento/genética , Defectos de los Tabiques Cardíacos/genética , Humanos , Lactante , Enfermedades del Nervio Óptico/genética , Linaje , Fenotipo , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
The importance of genetic counselling is being emphasized to an increasing degree, especially in view of advancements in the field of prenatal diagnosis and in methods of practical primary prevention. Genetic counselling is a process allowing specific information to be made available to clients in a specific manner. It only recently became apparent that knowledge about the process of the transmission of information in genetic counselling was inadequate and that re-evaluation was necessary. In genetic counselling communication is characterized by a distinctive type of psychodynamics in which philosophical, ethical and social factors and interrelations feature. An outline of the components of the communication process is provided. A model for the genetic counsellor's role in the comprehensive genetics team is suggested, and problem areas in the communication process are discussed.