Varones 46, XX: a propósito de dos casos genéticamente distintos / Males 46, XX: Presentation of Two Genetically Different Cases

Introducción Los desórdenes de diferenciación sexual son condiciones clínicas en las que existe una discrepancia entre el sexo cromosómico y el sexo fenotípico de un individuo. Esas condiciones suelen resultar angustiantes para los pacientes y sus familias e incluso para el equipo médico tratante debido a la dificultad en diagnosticarlas. Objetivo Presentar las características clínicas, genéticas y hormonales de dos varones con desórdenes de diferenciación sexual. Método Se realizó un estudio descriptivo basado en la revisión y análisis de datos de la historia clínica y la confrontación de los resultados con reportes similares. Resultados Se observaron dos individuos con fenotipo masculino y diagnóstico de hipogonadismo hipergonadotrófico con cariotipo 46, XX. El primer caso presentó testes pequeños y azoospermia, mientras que el segundo caso presentó baja talla, criptorquidea bilateral congénita y escrotos hipoplásicos. En ambos pacientes se exploró la presencia del gen SRY, confirmando su presencia en el primer caso y ausencia en el segundo caso. Conclusiones El diagnóstico genético-molecular actual apela a la combinación de técnicas tradicionales junto a técnicas modernas, como secuenciación por paneles genéticos a fin de identificar etiológicamente los desórdenes de diferenciación sexual. La presentación de esos casos aún se considera rara debido a su baja tasa de frecuencia poblacional, por lo que su reporte siempre resultará útil a la comunidad científica ya que muestran las distintas formas de presentación clínica y el manejo multidisciplinario de esos casos en diferentes contextos clínicos

Introduction Disorders of Sexual Development are clinical conditions in which a discrepancy between the chromosomal sex and the phenotypic sex occurs in an individual. These conditions are often distressing for patients and their families and even for the medical team due to the difficulty of diagnosing them. Objective The aim of this study was to present the clinical, genetic and hormonal characteristics of two males with sexual differentiation disorders. Method A descriptive study was performed based on the review and analysis of the clinical history data and the comparison of the results with similar cases reported. Results Two individuals with a male phenotype and a diagnosis of hypogonadotropic hypogonadism with 46, XX karyotype were observed. The first case presented small testes and azoospermia, while the second case presented low height, congenital bilateral cryptorchid and hypoplastic scrotums. The SRY gene was explored in both patients, and it was confirmed its presence in the first case and its absence in the second case. Conclusions The current molecular-genetic diagnosis calls for the combination of traditional techniques combined with modern techniques, such as the genetic panel sequencing, to identify etiologically the Disorders of Sexual Development. The presentation of these cases is even considered rare because of their low population frequency rate, so their report is always useful to the scientific community, for they show the different ways of the clinical disease presentation and the multidisciplinary management of these cases in different clinical contexts.

Novel EYA1 variants causing Branchio-oto-renal syndrome.

INTRODUCTION: Branchio-oto-renal (BOR) syndrome is an autosomal dominant genetic disorder characterized by second branchial arch anomalies, hearing impairment, and renal malformations. Pathogenic mutations have been discovered in several genes such as EYA1, SIX5, and SIX1. However, nearly half of those affected reveal no pathogenic variant by traditional genetic testing. METHODS AND MATERIALS: Whole Exome sequencing and/or Sanger sequencing performed in 10 unrelated families from Turkey, Iran, Ecuador, and USA with BOR syndrome in this study. RESULTS: We identified causative DNA variants in six families including novel c.525delT, c.979T > C, and c.1768delG and a previously reported c.1779A > T variants in EYA1. Two large heterozygous deletions involving EYA1 were detected in additional two families. Whole exome sequencing did not reveal a causative variant in the remaining four families. CONCLUSIONS: A variety of DNA changes including large deletions underlie BOR syndrome in different populations, which can be detected with comprehensive genetic testing.