High TGM1 Allelic Heterogeneity causing Lamellar ichthyosis in a small geographic area in South Mexico: Another Example of the "Réunion Paradox".

Lamellar ichthyosis (LI) is an autosomal recessive congenital ichthyosis characterized by generalized dry skin and severe scaling. It is caused by biallelic mutations in the TGM1 gene, however molecular data from non-Caucasian populations are limited. Results of genetic-molecular analysis of a group of LI pedigrees originating from two close small populations from south Mexico are presented. LI affected individuals belonging to 9 apparently unrelated families were studied. Exome sequencing or Sanger sequencing in probands from each family was carried out. Furthermore, DNA from 294 unaffected subjects from one of the communities were Sanger sequenced to determine the carrier frequency of the c.427C > T TGM1 variant. Five different TGM1 pathogenic variants, either in homozygous or in compound heterozygous state, were demonstrated in affected subjects. The two most common variants were c.427C > T (p.Arg143Cys) and c.1159+1G > T. A novel c.1645+1G > T TGM1 pathogenic allele was recognized. Carrier frequency analysis identified a total of 23 individuals heterozygous for the c.427C > T variant, predicting a prevalence of 78 carriers per 1000 inhabitants in the community. A high TGM1 allelic heterogeneity with 5 different LI-causing alleles in a limited geographic area was demonstrated. While the occurrence of homozygosity for a founder mutation is expected in small populations with high frequency of a particular autosomal recessive disorder, the occurrence of multiple pathogenic alleles has been previously described, a situation known as the Reúnion paradox. Our results expand the current knowledge of the mutational spectrum of TGM1-linked LI.

Case report: Disease phenotype associated with simultaneous biallelic mutations in ABCA4 and USH2A due to uniparental disomy of chromosome 1.

Inherited retinal diseases (IRDs) represent a spectrum of clinically and genetically heterogeneous disorders. Our study describes an IRD patient carrying ABCA4 and USH2A pathogenic biallelic mutations as a result of paternal uniparental disomy (UPD) in chromosome 1. The proband is a 9-year-old girl born from non-consanguineous parents. Both parents were asymptomatic and denied family history of ocular disease. Clinical history and ophthalmologic examination of the proband were consistent with Stargardt disease. Whispered voice testing disclosed moderate hearing loss. Next-generation sequencing and Sanger sequencing identified pathogenic variants in ABCA4 (c.4926C>G and c.5044_5058del) and USH2A (c.2276G>T). All variants were present homozygously in DNA from the proband and heterozygously in DNA from the father. No variants were found in maternal DNA. Further analysis of single nucleotide polymorphisms confirmed paternal UPD of chromosome 1. This is the first known patient with confirmed UPD for two recessively mutated IRD genes. Our study expands on the genetic heterogeneity of IRDs and highlights the importance of UPD as a mechanism of autosomal recessive disease in non-consanguineous parents. Moreover, a long-term follow-up is essential for the identification of retinal features that may develop as a result of USH2A-related conditions.

Tablet-based electroencephalography diagnostics for patients with epilepsy in the West African Republic of Guinea.

BACKGROUND AND PURPOSE: Epilepsy is most common in lower-income settings where access to electroencephalography (EEG) is generally poor. A low-cost tablet-based EEG device may be valuable, but the quality and reproducibility of the EEG output are not established. METHODS: Tablet-based EEG was deployed in a heterogeneous epilepsy cohort in the Republic of Guinea (2018-2019), consisting of a tablet wirelessly connected to a 14-electrode cap. Participants underwent EEG twice (EEG1 and EEG2), separated by a variable time interval. Recordings were scored remotely by experts in clinical neurophysiology as to data quality and clinical utility. RESULTS: There were 149 participants (41% female; median age 17.9 years; 66.6% ≤21 years of age; mean seizures per month 5.7 ± SD 15.5). The mean duration of EEG1 was 53 ± 12.3 min and that of EEG2 was 29.6 ± 12.8 min. The mean quality scores of EEG1 and EEG2 were 6.4 [range, 1 (low) to 10 (high); both medians 7.0]. A total of 44 (29.5%) participants had epileptiform discharges (EDs) at EEG1 and 25 (16.8%) had EDs at EEG2. EDs were focal/multifocal (rather than generalized) in 70.1% of EEG1 and 72.5% of EEG2 interpretations. A total of 39 (26.2%) were recommended for neuroimaging after EEG1 and 22 (14.8%) after EEG2. Of participants without EDs at EEG1 (n = 53, 55.8%), seven (13.2%) had EDs at EEG2. Of participants with detectable EDs on EEG1 (n = 23, 24.2%), 12 (52.1%) did not have EDs at EEG2. CONCLUSIONS: Tablet-based EEG had a reproducible quality level on repeat testing and was useful for the detection of EDs. The incremental yield of a second EEG in this setting was ~13%. The need for neuroimaging access was evident.

The epidemiology of patients treated at a private hospital as a consequence of the September 19th 2017 earthquake in Mexico City.

INTRODUCTION: Natural disasters can happen anytime. There is no gold standard for emergency department triaging and setup during these kind of emergencies. On September 19th 2017, at 13:14:40, a 7.1 magnitude on the Richter scale earthquake hit Mexico City. Buildings, including hospitals, collapsed. Our hospital offered free medical attention to those affected by the earthquake. MATERIAL AND METHODS: We reviewed the patient database for all patients who had been treated between September 19th and September 24th as a consequence of earthquake related injuries in both campuses. Age, gender, diagnosis, injured part, transportation method to hospital, triage color assigned in the emergency room, campus where attention was received, attention type, time spent in hospital, attention type. We calculated frequencies, medians, and standard deviation of lesions, triage code, and treatment in the emergency room. RESULTS: After the September 19th 2017 earthquake in Mexico City, our hospital treated 184 patients, most were female, most patients were between 21 and 60 years of age, the most common diagnosis were lower extremity trauma (no fractures), lower limb fractures, psychiatric disorders, craneoencephalic trauma and other upper extremity trauma. Most patients received a green triage and were discharged from the emergency department. CONCLUSION: Epidemiology of patients treated at our hospital is consistent with epidemiology reported in the literature for earthquake casualties. There was an adequate adaption of the emergency department for the reception and treatment of massive casualties. Patient records were mostly complete. We believe a standardized format designed specifically for these kinds of situations could be of great help in order to keep accurate patient records.

INTRODUCCIÓN: Los desastres naturales pueden ocurrir en cualquier momento. No existe un estándar de oro para el triaje y la configuración del Departamento de Urgencias durante este tipo de emergencias. El 19 de Septiembre de 2017, a las 13:14:40, un terremoto con magnitud 7.1 de la escala de Richter golpeó la Ciudad de México. Edificios, incluyendo hospitales, se derrumbaron. Nuestro hospital ofreció atención médica gratuita a los afectados por el terremoto. MATERIAL Y MÉTODOS: Revisamos la base de datos de pacientes que habían sido tratados entre el 19 y 24 de Septiembre como consecuencia de lesiones relacionadas con el terremoto en ambos campus. Fueron registrados edad, sexo, diagnóstico, lado lesionado, método de transporte al hospital, color de triaje asignado en la sala de urgencias, campus donde se recibió atención, tipo de atención, tiempo pasado en el hospital. Calculamos frecuencias, medianas y desviación estándar de lesiones, código de triaje y tratamiento en urgencias. RESULTADOS: Después del terremoto del 19 de Septiembre de 2017 en la Ciudad de México, nuestro hospital atendió a 184 pacientes, la mayoría eran mujeres, con una edad entre 21 y 60 años de edad, el diagnóstico más común fueron otros traumatismos en las extremidades inferiores (sin fracturas), fracturas de extremidades inferiores, trastornos psiquiátricos, trauma craneoencefálicos y otros traumatismos en las extremidades superiores. La mayoría de los pacientes recibieron un triaje verde y fueron dados de alta del departamento de emergencias. CONCLUSIÓN: La epidemiología de los pacientes tratados en nuestro hospital es consistente con la epidemiología reportada en la literatura por bajas causadas por terremotos. Hubo una adaptación adecuada del Servicio de Urgencias para la recepción y el tratamiento de las víctimas masivas. Los registros de los pacientes fueron, en su mayoría, completos. Creemos que un formato estandarizado diseñado específicamente para este tipo de situaciones podría ser de gran ayuda con el fin de mantener registros precisos del paciente.

[Patients' perceptions of and attitudes towards epilepsy surgery: mistaken concepts in Colombia]. / Percepciones y actitudes de los pacientes frente a la cirugia de la epilepsia: conceptos equivocados en Colombia.

INTRODUCTION: Selected patients with drug-resistant focal epilepsy benefit from epilepsy surgery, however significant delays remain. The aim of this study was to assess knowledge and attitudes toward epilepsy surgery among patients with epilepsy and identify barriers that might delay the treatment. PATIENTS AND METHODS: A 10-minute questionnaire was administered to patients with epilepsy in Colombia. Survey assessed the following: knowledge of surgical options, perceptions about the risks of surgery vs. ongoing seizures, disease disability, treatment goals, and demographic and socioeconomic variables. RESULTS: We recruited 88 patients with focal epilepsy. More than half of patients (56%) were not aware that surgery might be an option. Apprehension about epilepsy surgery was evident, 60% of patients perceived epilepsy surgery to be very or moderately dangerous. A large proportion of patients believe death (41%), stroke (47%), vision loss (56%), personality change (56%), paralysis (62%), difficulties in speaking (69%), and memory loss (60%) were frequent side effects. The majority of patients (62%) consider the surgical procedure as the last option of treatment. CONCLUSIONS: There is a negative attitude toward epilepsy surgery based on the patients' misperceptions of suffering neurological deficits during the surgery, reflecting lack of knowledge toward this type of treatment. These perceptions can contribute to delays in surgical care.

TITLE: Percepciones y actitudes de los pacientes frente a la cirugia de la epilepsia: conceptos equivocados en Colombia.Introduccion. Los pacientes con epilepsia focal farmacorresistente se podrian beneficiar de la cirugia de la epilepsia; sin embargo, existen demoras en la realizacion del procedimiento. El objetivo de este estudio fue evaluar el conocimiento y las actitudes de los pacientes hacia la cirugia de epilepsia e identificar barreras que pudieran retrasar el tratamiento. Pacientes y metodos. Se aplico un cuestionario de 10 minutos a pacientes con epilepsia en Colombia. La encuesta evaluo el conocimiento de la opcion quirurgica, las percepciones sobre el riesgo de la cirugia frente al riesgo de crisis no controladas, la discapacidad producida por la enfermedad, las metas del tratamiento y las variables demograficas y socioeconomicas. Resultados. Se seleccionaron 88 pacientes con epilepsia focal. El 56% de los pacientes no sabia que la cirugia podria ser una opcion terapeutica. El 60% considero que la cirugia de la epilepsia es muy o moderadamente peligrosa. Una gran proporcion pensaba que la muerte (41%), el ictus (47%), la perdida visual (56%), los cambios en la personalidad (56%), la paralisis (61%), las dificultades para hablar (69%) y la perdida de la memoria (60%) eran efectos secundarios comunes. La mayoria (62%) consideraba el procedimiento como la ultima opcion de tratamiento. Conclusiones. Existe una actitud negativa por parte de los pacientes frente a la cirugia de la epilepsia fundamentada en la sobreestimacion del riesgo de adquirir deficits neurologicos secundarios al procedimiento, lo que refleja la falta de conocimiento hacia este tratamiento. Estas percepciones erroneas pueden contribuir a demoras en la atencion quirurgica.

[Barriers impeding access to epilepsy surgery: a review of the literature]. / Barreras de acceso a la cirugia de la epilepsia: revision de la bibliografia.

Drug-resistant epilepsy, a chronic condition with long-term consequences can be treated with surgery. The efficacy and safety of surgery for temporal lobe epilepsy have been established through a large number of retrospective and prospective cohort studies and two randomized controlled clinical trials. Despite the excellent outcomes reported after surgery, the literature suggests that this procedure is an underutilized treatment. While evidence is lacking as to why epilepsy surgery is underused, cited reasons include: failure of primary care physicians and neurologists to provide information and identify patients who could be referred for surgery; different levels of technology at various centers, resulting in different candidate selection strategies; the belief that epilepsy surgery is a risky procedure and that it should be only viewed as the last option; patient preference to avoid surgery; parents wanting to wait until their child is old enough to participate in the decision-making process regarding surgery; unwillingness of insurers to cover the expenses associated with presurgical evaluations or lack of insurance; racial and social disparities, among others. In this paper we review the available epidemiological data about lack of utilization of epilepsy surgery.

TITLE: Barreras de acceso a la cirugia de la epilepsia: revision de la bibliografia.La epilepsia farmacorresistente es una condicion cronica con consecuencias a largo plazo que puede ser tratada quirurgicamente. La eficacia y la seguridad de la cirugia de la epilepsia del lobulo temporal se han establecido a traves de un gran numero de estudios de cohorte retrospectivos y prospectivos y dos ensayos clinicos controlados aleatorizados. A pesar de los excelentes resultados comunicados con la cirugia, la bibliografia sugiere que este procedimiento es un tratamiento subutilizado. Aunque no existe evidencia de esto, entre algunos de los motivos descritos se apuntan el fallo de los medicos de atencion primaria y los neurologos en proveer informacion, identificar y remitir a los pacientes a un centro de cirugia; los diferentes niveles de tecnologia en los centros, lo que provoca distintas estrategias de seleccion de los candidatos; la creencia de que la cirugia de la epilepsia es un procedimiento arriesgado que deberia contemplarse solo como ultima opcion; la preferencia del paciente por evitar la cirugia; el deseo de los padres de esperar hasta que sus hijos sean lo suficientemente mayores para participar en el proceso de toma de decisiones; el hecho de que las aseguradoras no cubran los gastos asociados con las evaluaciones prequirurgicas o la carencia de un seguro medico, y la desigualdad racial y social, entre otros. En este articulo se revisan los datos epidemiologicos disponibles en relacion con la falta de acceso a la cirugia de la epilepsia.

Familial exudative vitreoretinopathy: A report of an asymptomatic case with autosomal dominant inheritance detected using FZD4 molecular analysis. / Vitreorretinopatía exudativa familiar, reporte de un caso asintomático con herencia autosómica dominante, detectado mediante análisis molecular de FZD4.

OBJECTIVE: To report a familial case of Familial Exudative Vitreoretinopathy (FEVR) with an autosomal dominant inheritance pattern identified with the molecular analysis of FZD4. CASE REPORT: The proband is a 13 year-old boy who consulted for low vision. Fundus examination revealed a peripheral avascular zone and macular dragging, consistent with FEVR. Molecular analysis demonstrated a mutation of FZD4 in DNA from both the patient and his asymptomatic mother. DISCUSSION: This familial case was identified with the molecular analysis of FZD4 and shows the importance to explore first degree relatives in a sporadic FEVR case.

[Diagnosis and treatment of non-triggered single epileptic seizures]. / Diagnostico y tratamiento de la crisis epileptica unica no provocada.

Epileptic seizures are one of the main reasons for neurological visits in an emergency department. Convulsions represent a traumatic event for the patient and the family, with significant medical and social consequences. Due to their prevalence and impact, the initial management is of vital importance. Although following the first epileptic seizure, early recurrence diminishes after establishing treatment with antiepileptic drugs, the forecast for developing epilepsy and long-term outcomes are not altered by any early intervention. Detailed questioning based on the symptoms of the convulsions, the patient's medical history and a full electroencephalogram and neuroimaging study make it possible to define the risk of recurrence of the seizure and the possible diagnosis of epilepsy. Epileptic abnormalities, the presence of old or new potentially epileptogenic brain lesions, as well as nocturnal seizures, increase the risk of recurrence. Physicians must assess each patient on an individual basis to determine the most suitable treatment, and explain the risk of not being treated versus the risk that exists if treatment with antiepileptic drugs is established.

TITLE: Diagnostico y tratamiento de la crisis epileptica unica no provocada.Las crisis epilepticas son una de las principales causas de consulta neurologica en el servicio de urgencias. Un episodio convulsivo representa un evento traumatico para el paciente y la familia, con consecuencias medicas y sociales significativas. Por su prevalencia e impacto, el abordaje inicial es de vital importancia. Si bien despues de una primera crisis epileptica la recurrencia temprana disminuye con el inicio de farmacos antiepilepticos, el pronostico para el desarrollo de epilepsia y los desenlaces a largo plazo no se alteran por ninguna intervencion temprana. El interrogatorio detallado basado en la semiologia del episodio, los antecedentes del paciente y un estudio completo con electroencefalograma y neuroimagen permiten definir el riesgo de recurrencia de la crisis y el posible diagnostico de epilepsia. Las anormalidades epilepticas, la presencia de lesiones cerebrales con potencial epileptogeno antiguas o nuevas, asi como las crisis nocturnas, incrementan el riesgo de recurrencia. Los medicos deben evaluar a cada paciente de manera individual para determinar un tratamiento idoneo, explicando el riesgo de no tratar frente al riesgo existente con el inicio de farmacos antiepilepticos.

The relevance of neuropsychiatric symptoms and cognitive problems in new-onset epilepsy - Current knowledge and understanding.

Neurobehavioral and cognition problems are highly prevalent in epilepsy, but most research studies to date have not adequately addressed the precise nature of the relationship between these comorbidities and seizures. To address this complex issue and to facilitate collaborative, innovative research in the rising field of neurobehavioral comorbidities and cognition disturbances in new-onset epilepsy, international epilepsy experts met at the 3rd Halifax International Epilepsy Conference & Retreat at White Point, South Shore, Nova Scotia, Canada from September 18 to 20, 2014. This Conference Proceedings provides a summary of the conference proceedings. Specifically, the following topics are discussed: (i) role of comorbidities in epilepsy diagnosis and management, (ii) role of antiepileptic medications in understanding the relationship between epilepsy and neurobehavioral and cognition problems, and (iii) animal data and diagnostic approaches. Evidence to date, though limited, strongly suggests a bidirectional relationship between epilepsy and cognitive and psychiatric comorbidities. In fact, it is likely that seizures and neurobehavioral problems represent different symptoms of a common etiology or network-wide disturbance. As a reflection of this shared network, psychiatric comorbidities and/or cognition problems may actually precede the seizure occurrence and likely get often missed if not screened.

Clinical, imaging, and molecular findings in a sample of Mexican families with pantothenate kinase-associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder characterized by iron accumulation in the brain, because of mutations in the PANK2 gene. Phenotypic and genotypic characteristics of 11 patients from five Mexican families with PKAN disease are reported. Sequencing of PANK2 confirmed the diagnosis. The 11 patients had dysarthria associated with dystonia and Parkinsonism in six. Brain magnetic resonance imaging (MRI) showed the 'eye-of-the-tiger' sign in all patients. Three different mutations were identified, a novel one (p.A469P) and two (p.G219V and p.N404I) very rare. Homozygous sibs for the p.G219V mutation had a severe disease progression with early death. Dystonia predominated in the p.A469P/p.N404I compound heterozygous patients. Homozygous for p.N404I showed Parkinsonism, tics and personality and speech disorders. Early and late disease onset and variable expression was present in carriers of the different identified mutations. The 'eye-of-the-tiger' is an excellent neuroimaging hallmark to predict PANK2 mutations. We detected a 'cluster' of patients harboring the p.N404I mutation, strongly suggesting a founder effect for this mutation. This is the first familial clinical-genetic PKAN disease study accomplished in Mexico.

Frecuencia de dislipidemia y estado nutricional de escolares de áreas rurales paraguayas / Frequency of dislipidemia and nutritional state in schoolchildren of P a raguayan rural areas

Mundialmente la prevalencia de dislipidemias ha crecido en la última década en niños y adultos. En nuestro país las enfermedades circulatorias son la primera causa de muerte. Se determinó la frecuencia de dislipidemia, estado nutricional y factores asociados a dislipidemia en escolares de cuatro escuelas rurales públicas. Estudio observacional descriptivo de corte transverso en una población de escolares de 5 a 13 años de edad, de ambos sexos, con muestreo de casos consecutivos, realizado entre abril de 2008 a setiembre de 2009. Se determinó el estado nutricional por IMC según CDC 2000 y los niveles de colesterol y triglicéridos en sangre por métodos enzimáticos. A través de una encuesta, se consultaron los antecedentes familiares de dislipidemia, actividad física y hábitos alimentarios. El 59% de los 182 escolares incluidos en el estudio presentaron dislipidemia, 33% niveles de colesterol de riesgo moderado o alto, 41% niveles de triglicérido de riesgo moderado o alto. El 8% de los escolares mostró sobrepeso u obesidad. En cuanto a factores de riesgo asociados a dislipidemia, el 60% consumía carnes no magras al menos dos o tres veces por semana y el 56% de los niños que poseían padres con antecedentes de dislipidemia presentaban hipercolesterolemia de riesgo. La prevalencia de dislipidemia en esta población es preocupante y por ello, es necesario introducir estrategias dirigidas a mejorar los hábitos alimenticios en las instituciones educativas.

The worldwide prevalence of dislypidemiain children and adults has increased in the lastdecade.In our country, circulatory diseases are the first cause of death. The frequency ofdislypidemia, nutritional state and factors associated to dislypidemias in schoolchildren offour public rural schoolswas determined. This was a cross-sectional descriptiveobservational studywith consecutive samplingcarried out in a population of schoolboysand girlsaged5to13years oldfrom April 2008 to September 2009.The nutritional statewas determined by BMI according toCDC 2000and colesterol and triglycerides bloodlevels by enymatic methods. A survey collected family backgrounds about dislypidemia,physical activity and food habits.Fifty nine percent of the 182schoolchildren included inthe study presented dislypidemia, 33%had moderated or high risk for colesterol levelsand41%moderated or high risk for triglycerids levels while8%had overweight orobesity. In relation to risk factors associated to dislypidemia,60%ate lean meatat leasttwo to three times a week and56%of the children, who had parents with dislypidemiabackgrounds,showed risk hipercholesterolemia.The prevalence of dislypidemiafoundin this population is worrisomeshowing that it is necessary to introduce educationalstrategies aimed at improving food habits in the educational institutions.

Macular optical coherence tomography findings and GPR143 mutations in patients with ocular albinism.

The aim of this study was to describe macular findings using spectral-domain optical coherence tomography (SD-OCT) in patients with ocular albinism (OA) and their carrier mothers, and to identify the frequency of GPR143 gene mutations in these patients. The study included five patients with a clinical diagnosis of OA. SD-OCT of the macular area was performed in both patients and their mothers. The anatomical characteristics of the macula and retinal pigment epithelium (RPE), patterns of autofluorescence and infrared imaging were analyzed. Polymerase chain reaction amplification of the complete coding sequence of GPR 143 was performed and subsequently analyzed by direct sequencing in patients and their possible carrier mothers. SD-OCT images revealed the presence of inner retinal layers in the fovea, an abnormal disposition of the Henle layer and a lack of thickening in the perifoveal area. We found increased thickness in the RPE to the outer segment and in the outer segment to the outer nuclear layer that is associated with increased visual acuity. Autofluorescence images revealed an absence of normal hipoautofluorescence in the fovea. No changes were observed in the images of their carrier mothers. Mutation screening and sequence analysis of the GPR 143 gene revealed a novel pathological mutation in two patients. Abnormalities in the macula were observed in all patients. SD-OCT is a useful tool for the assessment of patients with OA. No changes were observed in the SD-OCT of carrier mothers. Only two patients had the GPR143 gene mutation.

A novel gene mutation in PANK2 in a patient with an atypical form of pantothenate kinase-associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) disease is an autosomal recessive neurodegenerative disorder with iron storage in the brain due to PANK2 gene mutations. Brain magnetic resonance imaging (MRI) shows the typical "eye-of-the-tiger" sign. The aim of the present study was to describe clinical, MRI and molecular findings in a 26-year-old male with atypical PKAN disease in whom, brain MRI scans showed bilateral pallidal T2-hypointensity with a small central region of T2-hyperintensity, resembling the "eye-of-the-tiger" typical image. Genetic analysis identified two mutations in PANK2: c.1561G>A and c.1663G>A, being the latter never described before. Due to limited phenotype-genotype correlation among patients with movement disorders, if "eye-of-the-tiger" brain MRI is present, PANK2 mutations investigation are needed to confirm PKAN disease.

Grado de Satisfacción de los médicos, que son usuarios del Dpto. de Análisis Clínicos del Instituto de Investigaciones en Ciencias de la Salud (UNA) durante el año 2010 / Degree of satisfaction of physicians using the services of the Department of Clinical Analysis of the Health Sciences Research Institute (UNA) during 2010

El Instituto de Investigaciones en Ciencias de la Salud depende de la Universidad Nacional de Asunción, es un establecimiento público con laboratorios que brinda a la comunidad servicios de rutina y especializados que satisfacen requisitos de calidad; los cuales son accesibles, seguros, confiables y confidenciales. La satisfacción del usuario médico es un indicador reconocido de calidad asistencial, es por ello que el Instituto ha elaborado un estudio de opinión con el objetivo de conocer el grado de satisfacción de los profesionales médicos con respecto al Departamento de Análisis Clínicos (AC) mediante una encuesta dirigida a los mismos y mejorar si fuese necesario el servicio brindado por el laboratorio. Se realizó un estudio observacional descriptivo de corte transverso, la selección de los médicos fue a partir de los pedidos de análisis que llegaron al Dpto. de AC durante el año 2010. Se utilizó como instrumento de medición una encuesta con 11 ítems y sugerencias, relacionadas con la satisfacción de los usuarios médicos. Los pedidos médicos solicitados fueron 68.9 % del Hospital de Clínicas y el 31.1% correspondieron a Centros de Salud del Ministerio de Salud Pública, Hospital de Policía, Hospital de las Fuerzas Armadas, entre otros. Del estudio de opinión se concluye que el grado de satisfacción de los médicos con respecto al Departamento de AC es bueno pero que es necesario insistir en aspectos de comunicación y colaboración entre los servicios clínicos y los laboratorios para que la mejora en el trabajo participativo de estos estamentos sea más fructífera.

A Novel De Novo EFNB1 Gene Mutation in a Mexican Patient with Craniofrontonasal Syndrome.

Craniofrontonasal syndrome (CNFS) is an X-linked disorder caused by mutations in the EFNB1 gene in which, paradoxically, heterozygous females are more severely affected than hemizygous males. In this paper, the clinical and molecular studies of a female subject with CFNS are described. A novel de novo c.473T>C (p.M158T) mutation in exon 3 of EFNB1 was demonstrated in this patient. The M158 residue of the Ephrin-B1 protein is highly conserved between species. Our results expand the mutational spectrum exposed by CNFS.

Immunophenotyping in peripheral blood mononuclear cells, aqueous humour and vitreous in a Blau syndrome patient caused by a novel NOD2 mutation.

The genetic and immunophenotypic characteristics of a 3-year-old patient with Blau syndrome (BS), an early onset sarcoidosis caused by mutations in NOD2, were investigated. Molecular analysis of NOD2 gene was achieved by PCR and direct nucleotide sequencing. Immunophenotyping included cytometric analysis of memory-effector markers on T-cells, and cytokine in serum, aqueous humour and vitreous. A novel M513R mutation in NOD2 was demonstrated. Immunophenotyping revealed higher frequency of CCR4+ cells and CCR9+ cells on CD4+ cells; most CD8+ cells were CCR7- and CCR9+. IL6 and IL-8 were detected in a gradient manner: vitreous humour>aqueous humour>serum. The immunophenotype in this patient was characterized by a differential expression of chemokine receptors on T cells and by a particular ocular microenvironment enriched in IL-6 and IL-8. To our knowledge, this is the first study analysing the immunological features of BS at aqueous humour, vitreous and blood levels. Our results expand the knowledge of the genetic and immunopathological basis of BS.

Novel sonic hedgehog mutation in a couple with variable expression of holoprosencephaly.

Holoprosencephaly (HPE) is the most common developmental defect of the forebrain and midface in humans. sporadic and inherited mutations in the human sonic hedgehog (SHH) gene cause 37% of familial HPE. A couple was referred to our unit with a family history of two spontaneous first trimester miscarriages and a daughter with HPE who presented early neonatal death. The father had a repaired median cleft lip, absence of central incisors, facial medial hypoplasia, and cleft palate. Intelligence and a brain CT scan were normal. Direct paternal sequencing analysis showed a novel nonsense mutation (W127X). Facial characteristics are considered as HPE microforms, and the pedigree suggested autosomal dominant inheritance with a variable expression of the phenotype. This study reinforces the importance of an exhaustive evaluation of couples with a history of miscarriages and neonatal deaths with structural defects.