Retinosquisis ligada al cromosoma X: presentación de un caso clínico y análisis del diagnóstico genético / X-linked Retinoschisis: a case report and genetic diagnosis analysis / Retinosquise ligada ao X: a presentação de um caso clínico e análise do diagnóstico genético

La Retinosquisis ligada al X, que se presenta fundamentalmente en varones, es una enfermedad genética caracterizada por agudeza visual reducida debido a degeneración macular. Su prevalencia es de 1/5000 varones en todo el mundo. Se manifiesta desde la primera década de la vida con pérdida de la visión que progresa hasta la adolescencia y se mantiene estable hasta la 4ta década de la vida, momento en que presenta un declive importante. El fondo de ojo suele mostrar esquisis. Las mujeres portadoras rara vez presentan síntomas. El gen involucrado es RS1, codifica para Retinosquina, proteína que participa en la integridad estructural y funcional de la retina. El mismo presenta diferentes mutaciones que generan pérdida de función de la proteína. La sospecha diagnóstica se basa en la clínica y los antecedentes familiares, y se apoya en la paraclínica confirmándose en la mayoría de los casos mediante secuenciación del gen. El tratamiento consiste en control periódico oftalmológico y cirugía de las complicaciones. Presentamos el caso de un niño de 2 años con episodios reiterados de desprendimiento de retina, con antecedentes familiares de Retinosquisis por línea materna en individuos de sexo masculino. Estos fueron estudiados demostrándose que son portadores de la variante probablemente patogénica c.466A>C (Arg156Gly) en el gen RS1 la cual había sido reportada previamente en una familia de origen chino. Se demostró que nuestro paciente presenta la mutación familiar en hemicigosis, por lo que esta es la segunda familia en que se confirma la segregación de esta variante con Retinosquisis.

X-linked Retinoschisis is a genetic disease characterized by reduced visual acuity mainly in men due to juvenile macular degeneration. Its prevalence is 1/5000 men worldwide. It manifests from the first decade of life with loss of vision that progresses to adolescence and then remains stable until the 4th decade of life, when it may present a significant decline. The fundus exam usually shows schism. Carrier women rarely have symptoms. The gene involved is RS1 (Xp22.13), which encodes for Retinoschisin, a protein that participates in the structural and functional integrity of the retina. In affected cases, mutations that generate loss of protein function were demonstrated. The diagnosis is based on the clinical and family history, and is supported by ophthalmology evaluation; in most cases it can be confirmed by sequencing of the gene. The treatment consists of periodic ophthalmological control and surgery of the complications. We describe the case of a 2 year old boy with repeated episodes of retinal detachment and who has a family history of Retinoschisis by maternal line in male individuals. These were studied, and it was shown that they are carriers of the probably pathogenic variant c.466A> C (Arg156Gly) in the RS1 gene, which had been reported previously in a family of Chinese origin. It was shown that our patient presents the family mutation in hemizygous state, so this is the second family in which the segregation of this variant with Retinoschisis is confirmed.

A retinosquise ligada ao X, que ocorre principalmente em homens, é uma doença genética caracterizada pela redução da acuidade visual devido à degeneração macular. Sua prevalência é de 1/5000 homens em todo o mundo. Manifesta-se desde a primeira década de vida com perda da visão que progride até a adolescência e permanece estável até a 4ª década de vida, época em que apresenta declínio significativo. O fundo geralmente mostra esquise. Portadoras do sexo feminino raramente apresentam sintomas. O gene envolvido é o RS1, que codifica a Retinosquina, proteína que participa da integridade estrutural e funcional da retina. Apresenta diferentes mutações que geram perda de função da proteína. A suspeita diagnóstica baseia-se na história clínica e familiar, e na paraclínica, sendo confirmada na maioria dos casos pelo sequenciamento gênico. O tratamento consiste em acompanhamento oftalmológico periódico e cirurgia para complicações. Apresentamos o caso de um menino de 2 anos com episódios repetidos de descolamento de retina, com história familiar de retinosquise materna no sexo masculino. Estes foram estudados mostrando que são portadores da variante provavelmente patogênica c.466A> C (Arg156Gly) no gene RS1, que havia sido relatado anteriormente em uma família de origem chinesa. Foi demonstrado que nosso paciente apresenta a mutação familiar em hemizigose, sendo esta a segunda família em que se confirma a segregação desta variante com Retinosquise.

Dyskeratosis congenita and a rare brain abscess / Disqueratosis congénita y absceso del sistema nervioso central

Abstract Dyskeratosis congenita is a rare inheritable disease which causes peculiar dermatological features and bone marrow failure with an increased risk of severe infections and neoplasia. Actinomyces spp. is part of the oral cavity flora. Invasive infections are mostly seen in immunocompromised hosts. We report a case of a rare central nervous infection and an underling inheritable disease.

Resumen La disqueratosis congénita es una enfermedad hereditaria, caracterizada por alteraciones cutáneas y aplasia medular. La principal causa de muerte son las infecciones y el desarrollo de neoplasias. Actinomices spp. son patógenos comensales de la cavidad oral y el tracto urinario, que en raras ocasiones suelen causar infecciones invasivas en el ser humano. Suelen ser más frecuentes en pacientes inmunocomprometidos o con mala higiene dental. Presentamos el caso de una lesión ocupante de espacio a nivel del sistema nervioso central con una inmuno deficiencia heredable.

Estallido respiratorio de neutrófilos por las técnicas del nitroazul tetrazolio (NBT) y dihidrorodamina (DHR) en niños con sospecha clínica de enfermedad granulomatosa crónica (EGC)

Introducción: El estallido respiratorio (ER) de neutrófilos es fundamental para la defensa contra infecciones, proceso ausente o ineficaz en la EGC, una inmunodeficiencia primaria (IDP) diagnosticada mediante la prueba del NBT. Actualmente se destacan las técnicas por citometría de flujo como la DHR, realizada únicamente en el Instituto de Investigaciones en Ciencias de la Salud (IICS), habiendo sido aplicada sólo en niños sanos. Objetivo: Evaluar el ER de neutrófilos por las técnicas NBT y DHR en niños con sospecha clínica de EGC y describir sus características clínico-demográficas. Materiales y Métodos: Se incluyeron 36 niños de ambos sexos, menores de 17 años de edad, remitidos al IICS entre el 2014-2015 por médicos especialistas. Se extrajo sangre para evaluación del ER de neutrófilos y se aplicó un cuestionario. Resultados: La mediana de edad fue de 4 años, 56% varones. Predominaron los pacientes hospitalizados, la sepsis y forunculosis cutánea fueron las manifestaciones clínicas más frecuentes y un 72% presentó recurrencia de infecciones con mediana de 3 episodios/año. El promedio para el IE de neutrófilos fue de 38,1±13,7 en el ensayo DHR, y 87±17% de activación para la prueba del NBT. En 8 pacientes los valores fueron inferiores al considerado normal y en un niño se confirmó EGC, observándose un patrón de herencia ligada al X. Conclusión: La evaluación del ER de neutrófilos permitió detectar un caso de EGC, determinándose el patrón hereditario mediante la técnica DHR por primera vez en el país. Es esencial el empleo de herramientas diagnósticas disponibles en niños con sospecha clínica de IDPs, para la detección y tratamiento oportunos que mejoran su calidad de vida y reducen la mortalidad.

Introduction: The neutrophil`s respiratory burst (RB) is essential for the defense against infections, this process is absent or ineffective in the CGD, a primary immunodeficiency (PID) diagnosed by the NBT test. Techniques that used flow cytometry such as DHR, performed only at the Instituto de Investigaciones en Ciencias de la Salud (IICS), currently stand out, having been applied only to healthy children. Objective: To evaluate the neutrophil`s RB using the NBT and DHR techniques in children with clinical suspicion of CGD and to describe their clinical and demographic characteristics. Materials and methods: 36 children of both sexes, with less than 17 years of age, that were referred to the IICS by specialists physicians between the years 2014-2015 were included. A blood sample was obtained to evaluate the neutrophil`s RB and a questionnaire was applied. Results: The median age was of 4 years and 56 % were males. Predominantly the patients were hospitalized, being sepsis and cutanueos furunculosis the most frequent clinical manifestations and a 72 % presented recurrent infection with a median of 3 episodes/year. The average for the neutrophil´s stimulation index (EI) was 38,1±13,7 with the DHR test, and 87±17% of activation for the NBT test. In 8 patients the values obtained were below the ones considered as normal and in one child CGD was confirmed, in which an X-linked inheritance pattern was observed. Conclusion: The evaluation of the neutrophil`s RB allowed the detection of one case of CGD, and the inheritance pattern was determined by the DHR test for the first time in our country. The use of available diagnostic tools in children with clinical suspicion of PID is essential for the appropriate detection and treatment that improve the quality of life and reduce mortality.

Mutation of Cx32 gene,clinical and electrophysiological features in patients with Charcot-Marie-Tooth disease / 临床神经病学杂志

Objective To investigate the mutation of Cx32 gene,clinical and electrophysiological features of Chinese patients with Charcot-Marie-Tooth(CMT) disease.Methods 24 CMT probands were selected for Cx32 mutation screening after the exclusion of the CMT1A 1.5 Mb duplication and male-to-male transmission.The motor and sensory nerve conduction studies were performed in all probands and most of their affected family members to establish the clinical CMT1,CMT2 or CMT intermediate diagnosis.The presence of mutations in the coding region of Cx32 was detected by single-strand conformation polymorphism analysis combined with direct sequencing.Results It was found 7 different point mutations in the coding region of Cx32 in 1 sporadic CMT1 patient and 6 X-linked inherited families,including 4 families with CMT1 diagnosis and 2 families with CMT intermediate diagnosis.There were 20 male CMTX patients,6 female CMTX patients and 12 asymptomatic female carriers among 38 family members bearing Cx32 mutation.All of the 26 patients were mildly to moderately affected clinically.Conclusions Seven different Cx32 point mutations were detected and the percentage of Chinese CMT families with Cx32 mutation is about 10% in our study.The inheritance model of CMT secondary to Cx32 mutation could be X-linked dominant,X-linked recessive or sporadic.Male patients are usually more severly affected than females with slower nerve conduction velocities.Cx32 mutation screening should be firstly performed in those CMT families without male-to-male transmission and CMT1A duplication.