RESUMO
(1) Background and objectives: Maturity-onset diabetes of the young (MODY) is a group of diabetes caused by gene defects related to insulin secretion. MODY1, MODY2, and MODY3 are the most common and account for approximately 80% of all cases. Other types are relatively rare. This study describes the clinical, analytical, and genetic characteristics of a patient with MODY10, and diabetic nephropathy, retinopathy, and functional hypogonadism diagnosis. (2) Materials and methods: A clinical case was analyzed and whole exome generation sequencing (WES) was used to detect mutations related to a monogenic variant. (3) Results: A seventeen-year-old male patient, who was diagnosed with apparent type 1 diabetes at the age of eight was started with insulin therapy. He came to the emergency room with glycemic decompensation, facial, and lower limb edema. During his evaluation, he had near-nephrotic range proteinuria of 2902 mg/24 h, a kidney ultrasound showing mild pyelocalyceal dilation, proliferative diabetic retinopathy, and was also diagnosed with functional hypogonadotropic hypogonadism. These comorbidities improved with adequate glycemic control. WES showed missense variant c.94G>A (p.Gly32Ser) in the INS gene, according to Clinvar corresponding to MODY10. It was a "de novo" variant not reported in his parents. (4) Conclusions: Monogenic diabetes (MD) is rare and MODY10 is among the less frequent types. MODY should be suspected in patients with type 1 phenotype with negative autoimmunity even in the absence of a family history of diabetes. To the best of our knowledge, we present here the first patient with these phenotypic traits of MODY10 reported in Latin America.
Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Retinopatia Diabética , Hipogonadismo , Humanos , Masculino , Retinopatia Diabética/genética , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Hipogonadismo/genética , Hipogonadismo/complicações , Adolescente , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/complicaçõesRESUMO
We aimed to assess the current genetics practice to manage patients with Lynch syndrome (LS) across Latin America. A Latin American LS survey was sent out to 52 centres/registries, comprising a total of 12 countries from the region. Overall, 33 centres completed the survey, of which the oldest LS registry was established in 1992 in Sao Paulo (Brazil), and the youngest this year in San Jose (Costa Rica). In total, 87% (26/30) of the participating centres/registries belonging to the nine countries are performing genetic testing. Overall, 1352 suspected families were sequenced. Pathogenic variants were identified in 34% of the families, with slightly differing distribution of variants between females and males. Path_MLH1 variants were identified in 39% of females and 50% of males (p = 0.023), while path_MSH2 were identified in 37% of females and males, followed by path_PMS2 in 11% of females and 8% of males, path_MSH6 in 13% of females and 3% of males (p < 0.001) and path_EPCAM in 0.3% of females and 2% of males. In Latin America, 9 of 12 (75%) participating countries had implemented healthcare for LS. LS screening is inconsistently applied within Latin America healthcare systems because of structural differences in the healthcare systems between the countries.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Predisposição Genética para Doença/genética , Testes Genéticos/métodos , Sistema de Registros/estatística & dados numéricos , Inquéritos e Questionários , Adulto , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Proteínas de Ligação a DNA/genética , Molécula de Adesão da Célula Epitelial/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , América do Sul , Adulto JovemRESUMO
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.