Deletion of exon 1 of the SLC16A2 gene: a common occurrence in patients with Allan-Herndon-Dudley syndrome.

BACKGROUND: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked type of mental retardation resulting from hindered thyroid hormone access to neurons. Clustered nonrecurrent deletions of SLC16A2 exon 1 have been described in three patients with AHDS. We report a fourth patient with such a deletion and discuss possible mechanisms leading to these rearrangements. CASE PRESENTATION: A three-and-a-half-year-old male with clinical and biochemical AHDS phenotype and a history of normal neonatal screening for hypothyroidism underwent SLC16A2 molecular analysis. Unexpectedly, he showed skeletal signs of hypothyroidism. METHODS AND RESULTS: The exons of the SLC16A2 (MCT8) gene and the sequences surrounding exon 1 were amplified using PCR. The patient had a 36-kb deletion affecting exon 1 of SLC16A2. The deletion junction was subjected to bioinformatic analyses, along with two other reported exon 1 deletion junctions, identifying possible sequence features and mechanisms responsible for such genomic rearrangements. DISCUSSION/CONCLUSION: This patient had a classic AHDS phenotype with an unexpectedly large anterior fontanel and delayed bone age and dentition. Bioinformatic analyses suggested that exon 1 deletions in patients with AHDS are caused by microhomology-mediated replicative-based and nonhomologous end-joining mechanisms. Rearrangement susceptibility may be due to the size of intron 1 and the percentage of repeat sequences.

Ultrasonographic description of brain cortex and cingulate sulcus development in Mexican neonates and infants with congenital hypothyroidism.

BACKGROUND: Ultrasonography of cortical and cingulum maturity patterns, were studied in newborns and infants with congenital hypothyroidism (CH). METHOD: Transversal study of 29 newborns and infants with CH, detected by neonatal screening and confirmed with thyroid function test, thyroid ultrasonography, and thyroid scintigraphy. During the first 2 months of life, transfontanelar brain ultrasonography was performed. Brain cortex maturity was assessed by normality referents provided by Slagle and Timor methods. RESULTS: Cortical immaturity signs were observed in 69% of infants (20 patients with Slage's method brain cortex development delay (Pearson's p=0.05). Logistic nominal analysis for normality prediction demonstrated a correlation between brain cortex development and age, bone age, treatment duration, and type of CH. The most sensitive detecting technique was sagittal sight by Slagle's method. CONCLUSIONS: Brain cortex delayed development is frequent in children with CH. Bone age, postnatal age at treatment start, and time since treatment start, correlates with neurological development, but not athyreosis or sublingual nodule.

Reguladores neuroendocrinos y gastrointestinales del apetito y la saciedad / Neuroendocrine and gastrointestinal modulators of appetite and satiety

Los estímulos conocidos con capacidad para actuar a nivel del hipotálamo, disminuyendo el apetito y aumentando el gasto de energía, proceden del sistema gastrointestinal (proteína similar al glucagón, polipéptido pancreático, péptido YY, colecistoquinina y oxintomodulina); del sistema endocrino (insulina, adrenalina a través de sus efectos beta-adrenérgicos y estrógenos); del tejido adiposo (leptina, visfatina, omentina-1, etc.); del sistema nervio-so periférico (efectos beta- adrenérgicos de la noradrenalina); y del sistema nervioso central (CRH, melanocortina, proteína agouti, CART y MCH). Aquéllos con capacidad para actuar sobre el hipotálamo para aumentar el apetito y disminuir el gasto energético proceden del sistema gastrointestinal (ghrelina y factor liberador de hormona de crecimiento), y del sistema nervioso central (neuropéptido Y, orexinas y canabinoides). En el hipotálamo se integran las señales aferentes neurales y humorales para coordinar la ingesta (a través de sensación de hambre o de saciedad) y el gasto energético (aumentando o disminuyendo el metabolismo basal y la eficacia termogénica del tejido adiposo pardo) en respuesta a condiciones que modifican el balance energético del organismo. El núcleo arcuato contiene 2 tipos de sistemas celulares, uno constituido por aquellas que disminuyen el apetito o neuronas que contienen proopiomelanocortina, que actúa como precursor de la hormona estimulante de los melanocitos-α y agonista de los receptores para melanocortina 3 y 4, y otro en el que se estimula el consumo de alimentos y contiene neuronas ricas en neuropéptido Y, y en péptido relacionado con la proteína agouti, que aumenta la ingesta de alimentos.

The modulators that diminish appetite and increase metabolic calorie needs at hypothalamus level are synthesized in different tissues: gastrointestinal system (glucagons-like peptide-1, pancreatic polypeptide, peptide YY, cholecystokinin and oxynt-modulin), the endocrine system (insulin, beta effects of adrenalin, and estrogens), adipose tissue (leptin, visfatin and omentin-1), peripheral nervous system (noradrenaline beta effects) and central nervous system (corticotropin released hormone, melanocortin, agouti protein, cocacine-amphetamine-regulated transcript and MCH). Those factors increasing appetite and lower basal metabolism comes from gastrointestinal system (ghrelin and growth hormone release hormone from pancreas), and central nervous system (neuropeptide Y, orexins and cannabinoids). In the hypothalamus, the neural and neuroendocrine afferents are integrated with the purpose of regulate appetite (hunger or satiety signals), and metabolic needs (increasing or decreasing basal metabolism and brown adipose tissue thermoregulation efficacy) according to body energy balance. The arcuate nucleus contains 2 main cellular systems: one rich in proopiomelanocortin (precursor of alpha melanocytes stimulating hormone and agonist of melanocortin 3 and 4 receptors), which decreases appetite, and other rich in neuropeptide Y and agoutirelated peptide which increase appetite.

Emotional dysfunction associated with diabetes in Mexican adolescents and young adults with type-1 diabetes.

OBJECTIVE: To assess the emotional dysfunction associated with diabetes in Mexican young individuals with type-1 diabetes. MATERIAL AND METHODS: A cross-sectional survey was conducted to perform a complete clinical and psychosocial evaluation of 93 consecutive type-1 diabetes patients, and 14 to 30 years. RESULTS: Adolescents had higher scores of emotional dysfunction related to diabetes and a diminished knowledge in diabetes-related areas. A multivariate logistic regression model showed that an inadequate emotional response to diabetes (high problem areas in diabetes or PAID scores) was mainly associated with a poor glycemic control (OR = 2.9, 95% CI 0.9-9.7, p = 0.09). Apprehension about the future and the possibility of serious complications had the highest mean PAID score in all age groups. CONCLUSIONS: New strategies should be developed to improve the routine care and support of young individuals with type-1 diabetes.

Emotional dysfunction associated with diabetes in Mexican adolescents and young adults with type-1 diabetes

OBJECTIVE: To assess the emotional dysfunction associated with diabetes in Mexican young individuals with type-1 diabetes. MATERIAL AND METHODS: A cross-sectional survey was conducted to perform a complete clinical and psychosocial evaluation of 93 consecutive type-1 diabetes patients, aged 14 to 30 years. RESULTS: Adolescents had higher scores of emotional dysfunction related to diabetes and a diminished knowledge in diabetes-related areas. A multivariate logistic regression model showed that an inadequate emotional response to diabetes (high problem areas in diabetes or PAID scores) was mainly associated with a poor glycemic control (OR=2.9, 95 percent CI 0.9-9.7, p=0.09). Apprehension about the future and the possibility of serious complications had the highest mean PAID score in all age groups. CONCLUSIONS: New strategies should be developed to improve the routine care and support of young individuals with type-1 diabetes

Estudio del paciente con genitales ambiguos / Patients with ambiguous genitalia

El estudio de un paciente con genitales ambiguos, requiere por lo menos 3 etapas de estudio. En la primera se deben identificar las alteraciones genitales, los antecedentes gestacionales y heredofamiliares, realizar un cariotipo en sangre periférica o en fibroblastos, determinar los niveles séricos de 17-OH progesterona y testosterona y realizar un ultrasonido abdominal y pélvico. En la segunda etapa se realizan pruebas de estimulación para demostrar la función gonadal y se determinan acciones enzimáticas y características de receptores hormonales. En ocasiones es necesario realizar una laparoscopia o una laparotomía. La tercera etapa requiere la identificación de los genes y hormonas involucrados en el proceso de diferenciación sexual

¿Es la obesidad el resultado de un epigenotipo equivocado? / Is obesity the consequence of an inadequate epigenotype?

Los individuos con obesidad asociada a sobrenutrición, manifiestan características genotípicas que modifican diversas funciones: Ingesta de alimentos condicionada por el ingreso calórico, composición de los macronutrientes, patabilidad, y control neuroendócrino del hambre y la saciedad; asimismo muestran una disminución en el egreso calórico producido por el metabolismo basal, el efecto térmico de los alimentos, el gasto calórico en ejercicio y la regulación de la termogénesis en situaciones de estrés. Existen además diferencias en la velocidad de oxidación de los nutrientes, tanto para cubrir las necesidades energéticas como para mantener la forma y la función. Es probable que muchos obesos, por seleción natural, presenten diferncias funcionales, algunas ocacionadas por mutaciones géneticas, que desde el punto de vista filogenético hayan facilitado la supervivencia de poblaciones nómadas y cazadoras con consumos alimentarios irregulares e inconstantes, pero que en la actualidad no sólo son innecesarias, sino que su asociación con sobrenutrición aumenta la morbimortalidad