Whole Exome Sequencing of 20 Spanish Families: Candidate Genes for Non-Syndromic Pediatric Cataracts.

Non-syndromic pediatric cataracts are defined as opacification of the crystalline lens that occurs during the first years of life without affecting other organs. Given that this disease is one of the most frequent causes of reversible blindness in childhood, the main objective of this study was to propose new responsible gene candidates that would allow a more targeted genetic approach and expand our genetic knowledge about the disease. We present a whole exome sequencing (WES) study of 20 Spanish families with non-syndromic pediatric cataracts and a previous negative result on an ophthalmology next-generation sequencing panel. After ophthalmological evaluation and collection of peripheral blood samples from these families, WES was performed. We were able to reach a genetic diagnosis in 10% of the families analyzed and found genes that could cause pediatric cataracts in 35% of the cohort. Of the variants found, 18.2% were classified as pathogenic, 9% as likely pathogenic, and 72.8% as variants of uncertain significance. However, we did not find conclusive results in 55% of the families studied, which suggests further studies are needed. The results of this WES study allow us to propose LONP1, ACACA, TRPM1, CLIC5, HSPE1, ODF1, PIKFYVE, and CHMP4A as potential candidates to further investigate for their role in pediatric cataracts, and AQP5 and locus 2q37 as causal genes.

Molecular and Genetic Mechanism of Non-Syndromic Congenital Cataracts. Mutation Screening in Spanish Families.

Our purpose was to identify mutations responsible for non-syndromic congenital cataracts through the implementation of next-generation sequencing (NGS) in our center. A sample of peripheral blood was obtained from probands and willing family members and genomic DNA was extracted from leukocytes. DNA was analyzed implementing a panel (OFTv2.1) including 39 known congenital cataracts disease genes. 62 probands from 51 families were recruited. Pathogenic or likely pathogenic variants were identified in 32 patients and 25 families; in 16 families (64%) these were de novo mutations. The mutation detection rate was 49%. Almost all reported mutations were autosomal dominant. Mutations in crystallin genes were found in 30% of the probands. Mutations in membrane proteins were detected in seven families (two in GJA3 and five in GJA8). Mutations in LIM2 and MIP were each found in three families. Other mutations detected affected EPHA2, PAX6, HSF4 and PITX3. Variants classified as of unknown significance were found in 5 families (9.8%), affecting CRYBB3, LIM2, EPHA2, ABCB6 and TDRD7. Mutations lead to different cataract phenotypes within the same family.

Doctor Antonio Alfaro's notes in the treaty by Desault and Bichat. First urological work in Spanish in the XIX Century.

OBJECTIVES: We performed a study on the notes made by doctor Antonio Alfaro to the book by Bichat and Desault "Treaty of urinary tract diseases". RESULTS: Such notes are altogether more extensive than the work they accompany. In them we see the knowledge about the treatment of urinary tract diseases in the beginning of the XIX century had a great level and, at least, similar to that of other European countries. The notes are accompanied by multiple references to surgeons of various times, and publications of that time. All them conform a real Urology text with its own personality. CONCLUSIONS: Dr. Antonio Alfaro must be among the Spanish urological medical literature authors of the 19th Century.

Las anotaciones del doctor Antonio Alfaro al tratado de Desault y Bichat. Primera obra urológica en castellano del siglo XIX / Doctor Antonio Alfaro`s notes in the treaty by Desault and Bichat. First urological work in Spanish in the XIX Century

OBJETIVO: Realizamos el estudio de las anotaciones que hace el Doctor Antonio Alfaro, a la obra de Bichat y Desault ‘‘Tratado de las enfermedades de las vías urinarias’’. RESULTADO: Dichas anotaciones son en conjunto más extensas que la obra a la que acompañan. En ellas se aprecia que los conocimientos en el tratamiento de enfermedades de aparato urinario, eran, a principios de siglo XIX, de gran nivel y al menos semejante al existente en otros países Europeos. Las anotaciones van acompañadas de multitud de referencias de cirujanos de diversas épocas, y a publicaciones del momento. Todo ello conforma un autentico texto de Urología con personalidad propia. CONCLUSIONES: D. Antonio Alfaro debe formar parte de los autores de literatura médica urológica española, del siglo XIX (AU)

OBJECTIVES: We performed a study on the notes made by doctor Antonio Alfaro to the book by Bichat and Desault “Treaty of urinary tract diseases”. RESULTS: Such notes are altogether more extensive than the work they accompany. In them we see the knowledge about the treatment of urinary tract diseases in the beginning of the XIX century had a great level and, at least, similar to that of other European countries. The notes are accompanied by multiple references to surgeons of various times, and publications of that time. All them conform a real Urology text with its own personality. CONCLUSIONS: Dr. Antonio Alfaro must be among the Spanish urological medical literature authors of the 19th Century (AU)