Role of PIGM and PIGX in glycosylphosphatidylinositol biosynthesis and human health (Review).

Glycosylphosphatidylinositol-glycan (GPI) is an anchor to specific cell surface proteins known as GPI-anchored proteins (APs) that are localized in lipid rafts and may act as cell co-receptors, enzymes and adhesion molecules. The present review investigated the significance of GPI biosynthesis class phosphatidylinositol-glycan (PIG)M and PIGX in GPI synthesis and their implications in human health conditions. PIGM encodes GPI-mannosyltransferase I (MT-I) enzyme that adds the first mannose to the GPI core structure. PIGX encodes the regulatory subunit of GPI-MT-I. The present review summarizes characteristics of the coding sequences of PIGM and PIGX, and their expression in humans, as well as the relevance of GPI-MT-I and the regulatory subunit in maintaining the presence of GPI-APs on the cell surface and their secretion. In addition, the association of PIGM mutations with paroxysmal nocturnal hemoglobinuria and certain types of GPI-deficiency disease and the altered expression of PIGM and PIGX in cancer were also reviewed. In addition, their interaction with other proteins was described, suggesting a complex role in cell biology. PIGM and PIGX are critical genes for GPI synthesis. Understanding gene and protein regulation may provide valuable insights into the role of GPI-APs in cellular processes.

Fragile X Syndrome in children.

Fragile X syndrome is caused by the expansion of CGG triplets in the FMR1 gene, which generates epigenetic changes that silence its expression. The absence of the protein coded by this gene, FMRP, causes cellular dysfunction, leading to impaired brain development and functional abnormalities. The physical and neurologic manifestations of the disease appear early in life and may suggest the diagnosis. However, it must be confirmed by molecular tests. It affects multiple areas of daily living and greatly burdens the affected individuals and their families. Fragile X syndrome is the most common monogenic cause of intellectual disability and autism spectrum disorder; the diagnosis should be suspected in every patient with neurodevelopmental delay. Early interventions could improve the functional prognosis of patients with Fragile X syndrome, significantly impacting their quality of life and daily functioning. Therefore, healthcare for children with Fragile X syndrome should include a multidisciplinary approach.

El síndrome de X frágil es causado por la expansión de tripletas CGG en el gen FMR1, el cual genera cambios epigenéticos que silencian su expresión. La ausencia de la proteína codificada por este gen, la FMRP, causa disfunción celular, llevando a deficiencia en el desarrollo cerebral y anormalidades funcionales. Las manifestaciones físicas y neurológicas de la enfermedad aparecen en edades tempranas y pueden sugerir el diagnóstico. Sin embargo, este debe ser confirmado por pruebas moleculares. El síndrome afecta múltiples aspectos de la vida diaria y representa una alta carga para los individuos afectados y para sus familias. El síndrome de C frágil es la causa monogénica más común de discapacidad intelectual y trastornos del espectro autista; por ende, el diagnóstico debe sospecharse en todo paciente con retraso del neurodesarrollo. Intervenciones tempranas podrían mejorar el pronóstico funcional de pacientes con síndrome de X frágil, impactando significativamente su calidad de vida y funcionamiento. Por lo tanto, la atención en salud de niños con síndrome de X frágil debe incluir un abordaje multidisciplinario.

Fragile X Syndrome in children

Fragile X syndrome is caused by the expansion of CGG triplets in the FMR1 gene, which generates epigenetic changes that silence its expression. The absence of the protein coded by this gene, FMRP, causes cellular dysfunction, leading to impaired brain development and functional abnormalities. The physical and neurologic manifestations of the disease appear early in life and may suggest the diagnosis. However, it must be confirmed by molecular tests. It affects multiple areas of daily living and greatly burdens the affected individuals and their families. Fragile X syndrome is the most common monogenic cause of intellectual disability and autism spectrum disorder; the diagnosis should be suspected in every patient with neurodevelopmental delay. Early interventions could improve the functional prognosis of patients with Fragile X syndrome, significantly impacting their quality of life and daily functioning. Therefore, healthcare for children with Fragile X syndrome should include a multidisciplinary approach.

El síndrome de X frágil es causado por la expansión de tripletas CGG en el gen FMR1, el cual genera cambios epigenéticos que silencian su expresión. La ausencia de la proteína codificada por este gen, la FMRP, causa disfunción celular, llevando a deficiencia en el desarrollo cerebral y anormalidades funcionales. Las manifestaciones físicas y neurológicas de la enfermedad aparecen en edades tempranas y pueden sugerir el diagnóstico. Sin embargo, este debe ser confirmado por pruebas moleculares. El síndrome afecta múltiples aspectos de la vida diaria y representa una alta carga para los individuos afectados y para sus familias. El síndrome de C frágil es la causa monogénica más común de discapacidad intelectual y trastornos del espectro autista; por ende, el diagnóstico debe sospecharse en todo paciente con retraso del neurodesarrollo. Intervenciones tempranas podrían mejorar el pronóstico funcional de pacientes con síndrome de X frágil, impactando significativamente su calidad de vida y funcionamiento. Por lo tanto, la atención en salud de niños con síndrome de X frágil debe incluir un abordaje multidisciplinario.

2q37 deletion syndrome in a Colombian patient with macrocephaly: a case report.

BACKGROUND: 2q37 deletion syndrome is a rare autosomal dominant disorder caused by deletions in the 2q37 cytobands leading to developmental delay, intellectual disability, behavioral abnormalities and dysmorphic craniofacial features with more than 115 patients described worldwide. CASE PRESENTATION: We describe a Colombian 3-year-old patient with verbal communication delay, umbilical hernia, facial dysmorphic features, hypotonia, and macrocephaly with normal magnetic resonance imaging. Microarray-based comparative genomic hybridization revealed a 5.9 Mb deletion in the 2q37.2 and 2q37.3 regions, eliminating 60 protein-coding genes in one of her chromosomes 2 and allowing the diagnosis of 2q37 deletion syndrome in this patient. Therapeutic interventions so far were the surgical correction of the umbilical hernia. CONCLUSIONS: Genetic tests are important tools for the diagnosis of clinically complex and infrequent conditions but also for timely diagnosis that allows appropriate surveillance, interventions, and genetic counseling. This case also provides information for expanding the phenotypical and genetic characterization of 2q37 deletion syndrome.

Structural Protein Effects Underpinning Cognitive Developmental Delay of the PURA p.Phe233del Mutation Modelled by Artificial Intelligence and the Hybrid Quantum Mechanics-Molecular Mechanics Framework.

A whole-exome capture and next-generation sequencing was applied to an 11 y/o patient with a clinical history of congenital hypotonia, generalized motor and cognitive neurodevelopmental delay, and severe cognitive deficit, and without any identifiable Syndromic pattern, and to her parents, we disclosed a de novo heterozygous pathogenic mutation, c.697_699del p.Phe233del (rs786204835)(ACMG classification PS2, PM1, PM2, PP5), harbored in the PURA gene (MIM*600473) (5q31.3), associated with Autosomal Dominant Mental Retardation 31 (MIM # 616158). We used the significant improvement in the accuracy of protein structure prediction recently implemented in AlphaFold that incorporates novel neural network architectures and training procedures based on the evolutionary, physical, and geometric constraints of protein structures. The wild-type (WT) sequence and the mutated sequence, missing the Phe233, were reconstructed. The predicted local Distance Difference Test (lDDT) for the PURAwt and the PURA-Phe233del showed that the occurrence of the Phe233del affects between 220-320 amino acids. The distortion in the PURA structural conformation in the ~5 Å surrounding area after the p.Phe233del produces a conspicuous disruption of the repeat III, where the DNA and RNA helix unwinding capability occurs. PURA Protein-DNA docking corroborated these results in an in silico analysis that showed a loss of the contact of the PURA-Phe233del III repeat domain model with the DNA. Together, (i) the energetic and stereochemical, (ii) the hydropathic indexes and polarity surfaces, and (iii) the hybrid Quantum Mechanics-Molecular Mechanics (QM-MM) analyses of the PURA molecular models demarcate, at the atomic resolution, the specific surrounding region affected by these mutations and pave the way for future cell-based functional analysis. To the best of our knowledge, this is the first report of a de novo mutation underpinning a PURA syndrome in a Latin American patient and highlights the importance of predicting the molecular effects in protein structure using artificial intelligence algorithms and molecular and atomic resolution stereochemical analyses.

Síndrome X frágil y otras patologías asociadas al gen FMR1 / Fragile X Syndrome and Other Pathologies Associated with the FMR1 Gene / Síndrome do X frágil e outras patologias associadas ao gene FMR1

Resumen: el síndrome X frágil es la causa más frecuente de retraso psicomotor vinculado al cromosoma X en niños, con una prevalencia de 1 : 5.000 en hombres y 1 : 4.000 - 8.000 en mujeres. Además, es la causa hereditaria más asociada al síndrome del espectro autista. Esta patología posee como base etiológica la expansión del triplete CGG en el extremo distal del gen FMR1, lo que causa su silenciamiento. Los pacientes afectados con este síndrome suelen padecer de problemas conductuales, neurológicos, cardíacos y ortopédicos. Este síndrome también se relaciona con la insuficiencia ovárica primaria asociada al X frágil, y el síndrome de temblor y ataxia asociado al X frágil que afectan a la madre y al abuelo materno, y que, por su reciente descripción, podrían ser desconocidos por el personal sanitario, lo que retrasa su diagnóstico y tratamiento. El objetivo de este artículo es analizar estas enfermedades, con el fin de describir el conocimiento actual sobre su etiología, las manifestaciones clínicas, el diagnóstico y el tratamiento. Esto se realizó mediante la recopilación de artículos en Pubmed, con algunas contribuciones de las bases de datos Scielo, Redalyc, Europe PMC, Science Direct, Google Académico y Genetics Home Reference. Entre las conclusiones principales se destaca que los fenotipos asociados a la premutación del gen FMR1 contemplan mecanismos fisiopatológicos diferentes al síndrome X frágil, a pesar de estar íntimamente relacionados.

Abstract: fragile X syndrome is the most common cause of X-linked psychomotor retardation in children, with a prevalence of 1 : 5.000 in males and 1 : 4.000 -8.000 in females. It is also the hereditary cause most associated with autism spectrum syndrome. The etiological basis of this pathology is the expansion of the CGG triplet at the distal end of the FMR1 gene, which causes its silencing. Patients affected with this syndrome usually suffer from behavioral, neurological, cardiac and orthopedic problems. This syndrome is also related to Fragile X-associated primary ovarian insufficiency, and Fragile X-associated tremor and ataxia syndrome affecting the mother and maternal grandfather, which, because of their recent description, may be unknown to health care providers, delaying their diagnosis and treatment. The objective of this article is to analyze these diseases, in order to describe the current knowledge about their etiology, clinical manifestations, diagnosis and treatment. This was done by collecting articles in Pubmed, with some contributions from Scielo, Redalyc, Europe PMC, Science Direct, Google Scholar and Genetics Home Reference databases. Among the main conclusions, it is highlighted that the phenotypes associated with FMR1 gene premutation involve different pathophysiological mechanisms to Fragile X syndrome, despite being closely related.

Resumo: a síndrome do X frágil é a causa mais comum de retardo psicomotor ligado ao cromossomo X em crianças, com prevalência de 1 : 5.000 em homens e 1 : 4.000 a 8.000 em mulheres. Além disso, é a causa mais hereditária associada à síndrome do espectro do autismo. Essa patologia tem como base etiológica a expansão do trigêmeo CGG na extremidade distal do gene FMR1, o que causa seu silenciamento. Pacientes com essa síndrome geralmente sofrem de problemas comportamentais, neurológicos, cardíacos e ortopédicos. Essa síndrome também está relacionada à insuficiência ovariana primária associada ao X frágil, à síndrome do tremor e à ataxia associada ao X frágil, que acometem a mãe e o avô materno, e que, devido à sua descrição recente, poderiam ser desconhecidas pelos profissionais de saúde, o que atrasa seu diagnóstico e tratamento. O objetivo deste artigo é analisar essas doenças, a fim de descrever o conhecimento atual sobre sua etiologia, manifestações clínicas, diagnóstico e tratamento. Isso foi feito através da recopilação de artigos no Pubmed, com algumas contribuições das bases de dados Scielo, Redalyc, Europe PMC, Science Direct, Google Academic e Genetics Home Reference. Dentre as principais conclusões, destaca-se que os fenotipos associados à premutação do gene FMR1 incluem outros mecanismos fisiopatológicos além da síndrome do X frágil, apesar de eles estarem intimamente relacionados.

Evidence of GMPPA founder mutation in indigenous Guatemalan population associated with alacrima, achalasia, and mental retardation syndrome.

Congenital disorders of glycosylation (CDG) are a heterogeneous group of inborn errors of metabolism mostly causing multisystem disease. In 2013, biallelic mutations in the GMPPA gene were described in association with one such CDG known as alacrima, achalasia, and mental retardation syndrome (AAMR). To date, 18 patients have been reported, nearly all displaying the same pathognomonic triad of symptoms described in the name. This condition shares considerable phenotypic overlap with Triple-A syndrome caused by biallelic mutations in the AAAS gene; however, AAMR lacks the characteristic adrenocortical findings associated with Triple-A syndrome. We report three patients from two unrelated families with the same homozygous GMPPA mutation (c.265dup, p.L89fs). Notably, both families reported indigenous Maya-Mam heritage and originated from the town of Concepción Chiquirichapa in Quezaltenango, Guatemala. Our cases help to expand the AAMR phenotype by outlining dysmorphic features not well described in the prior cases. Additionally, we encourage all providers with patients presenting with this unique triad of symptoms to consider sequencing of the GMPPA gene. Special consideration should be given to families of Guatemalan Maya-Mam ancestry who may also have this identified founder mutation. Finally, this condition may indeed be underdiagnosed based on a review of the literature.

Complejo esclerosis tuberosa en población aymara: relato de un caso / Tuberous sclerosis complex in the Aymara population: a case report

El Complejo Esclerosis Tuberosa (CET) es una enfermedad de origen genético, multisistémica de transmisión autosómica dominante, se debe a la mutación de los genes TSC1 (Tuberose Sclerosis Complex 1) y TSC2 de los cromosomas 9 y 16 respectivamente. Las manifestaciones clínicas se deben a la presencia de lesiones tumorales benignas (harmatomas) en diferentes órganos lo que genera un amplio espectro de signos y síntomas. El caso que se presenta es de una adolescente de origen aymara con epilepsia, retraso mental y lesiones dérmicas típicas. Es una enfermedad poco frecuente en nuestro medio y rara en personas de origen indígena, no encontrándose ninguna descripción en la literatura nacional. Por la multiplicidad de las manifestaciones clínicas, se hace necesario divulgar la información para que que las diferentes especialidades médicas reconozcan y diagnostiquen esta patología tempranamente para un tratamiento adecuado, oportuno y interdisciplinar.

The Tuberose Sclerosis Complex (TSC) is a genetic, multisystemic disease of autosomal dominant transmission, due to the mutation of the TSC1 and TSC2 genes of chromosomes 9 and 16 respectively. The clinical manifestations are due to the presence of benign tumor lesions (harmatomas) in different organs, which generates a wide spectrum of signs and symptoms. The case presented is that of a teenager of Aymara origin with epilepsy, mental retardation and typical skin lesions. It is a rare disease in our environment and rare in people of indigenous origin, no description found in the national literature. Due to the multiplicity of the clinical manifestations, it is necessary to disseminate the information so that the different medical specialties recognize and diagnose this pathology early for an adequate, timely and interdisciplinary treatment.

Repercusión familiar de los diagnósticos de retraso mental leve y trastorno de conducta / Family Repercussion of the Diagnoses of Mild Mental Retardation and Conduct Behavior

Introducción: Los diagnósticos de retraso mental leve y trastorno de conducta son eventos paranormativos con grandes posibilidades de repercusión familiar. La investigación que se realizó es novedosa pues no existen antecedentes de estudios en los que se comparen los resultados de ambas entidades diagnósticas. Se asumió como principal sustento teórico la propuesta que realizara Patricia Herrera Santí en su tesis doctoral de 2010, enriquecida junto a Idarmis González (2013). Objetivo: Determinar la repercusión familiar de los diagnósticos de retraso mental leve y trastorno de la conducta en el período comprendido entre octubre y noviembre de 2015. Métodos: Se realizó un estudio de tipo descriptivo con un diseño de investigación no experimental y una metodología mixta o cuanti-cualitativa. La muestra estuvo conformada por 20 familias, dividida a su vez en dos submuestras de 10 familias cada una, la primera contaba entre sus miembros con un menor diagnosticado de retraso mental leve, y la segunda la integraban otras 10 familias con un miembro diagnosticado con trastorno de la conducta. Se aplicó el Instrumento de Repercusión Familiar y una entrevista semi-estructurada. Resultados: El nivel de repercusión general fue moderado en su mayoría en ambas categorías diagnósticas, predominando un sentido de la repercusión desfavorable y un impacto predisponente a la afectación de la salud familiar. Conclusiones: Los diagnósticos de retraso mental leve y trastorno de conducta repercutieron en las familias evaluadas, exigiendo en estas algunos cambios en su dinámica interna y modo de vida(AU)

Introduction: The diagnoses of mild mental retardation and conduct disorder are paranormative events with great possibilities of family repercussion. The research conducted is novel because there are no previous studies comparing the results of both diagnostic entities. The proposal that Patricia Herrera Santí presents in her 2010 doctoral dissertation was assumed as the main theoretical support, enriched together with Idarmis González (2013). Objective: To determine the family repercussion of the diagnoses of mild mental retardation and conduct disorder in the period between October and November 2015. Methods: A descriptive study was carried out with a non-experimental research design and a mixed or quantitative-qualitative methodology. The sample consisted of 20 families, divided in turn into two subsamples of 10 families each, the first had among its members a minor diagnosed with mild mental retardation, while the second was composed of 10 other families with a member diagnosed with conduct disorder. The Family Repercussion Instrument and a semi-structured interview were applied. Results: The level of general repercussion was mostly moderate in both diagnostic categories, with a predominance of unfavorable repercussions and a predisposing repercussion on family health. Conclusions: The diagnoses of mild mental retardation and conduct disorder affected the families evaluated, demanding from these some changes in their internal dynamics and way of life(AU)

Snyder-Robinson syndrome.

Snyder-Robinson syndrome, also known as spermine synthase deficiency, is an X-linked intellectual disability syndrome (OMIM #390583). First described by Drs. Snyder and Robinson in 1969, this syndrome is characterized by an asthenic body habitus, facial dysmorphism, broad-based gait, and osteoporosis with frequent fractures. We report here a pediatric autopsy of a 4 year old male with a history of intellectual disability, gait abnormalities, multiple fractures, and seizures previously diagnosed with Snyder-Robinson syndrome with an SMS gene mutation (c.831G>T:p.L277F). The cause of death was hypoxic-ischemic encephalopathy secondary to prolonged seizure activity. Although Snyder-Robinson syndrome is rare, the need to recognize clinical findings in order to trigger genetic testing has likely resulted in under diagnosis.

Snyder-Robinson syndrome

Snyder-Robinson syndrome, also known as spermine synthase deficiency, is an X-linked intellectual disability syndrome (OMIM #390583). First described by Drs. Snyder and Robinson in 1969, this syndrome is characterized by an asthenic body habitus, facial dysmorphism, broad-based gait, and osteoporosis with frequent fractures. We report here a pediatric autopsy of a 4 year old male with a history of intellectual disability, gait abnormalities, multiple fractures, and seizures previously diagnosed with Snyder-Robinson syndrome with an SMS gene mutation (c.831G>T:p.L277F). The cause of death was hypoxic-ischemic encephalopathy secondary to prolonged seizure activity. Although Snyder-Robinson syndrome is rare, the need to recognize clinical findings in order to trigger genetic testing has likely resulted in under diagnosis.

Enfermedad de Darier white: Reporte de caso y relación con enfermedades neuropsiquiátricas / Darier white disease: Case report and relationship with neuropsychiatric diseases

La enfermedad de Darier White es una enfermedad autosómica dominante, de penetrancia completa con expresividad variable que afecta al cromosoma 12q23-24.1. Se caracteriza por manifestaciones dermatológicas como: placas o pápulas no foliculares en zonas seborreicas, que tienen un olor característico. La presente investigación busca presentar reportes de casos de dos pacientes, en un Hospital Universitario en Bogotá-Colombia y la relación que existe con enfermedades psiquiátricas, tales como: trastorno afectivo bipolar y retraso mental. Se realizó una historia clínica y examen físico completo. Posteriormente, se firmó un consentimiento informado para toma de fotos y uso de las mismas, con fines educativos. Con estos elementos, se buscó información en las bases de datos más requeridas hoy en día, como: Pubmed, Science Direct, Embase y Scielo utilizando búsquedas con palabras claves, relacionando enfermedad de Darier White y enfermedades psiquiátricas en general. Consecutivamente, se buscó información de trastorno afectivo bipolar y retraso mental. En definitiva se enfocó cada uno de los casos descritos, como enfermedad de Darier con la asociación clínica de enfermedades psiquiátricas, en relación con el trastorno afectivo bipolar y retraso mental, con los que esta enfermedad muestra una relación estrecha.

Darier White or dyskeratosis follicularis disease is a genetic disorder of autosomal dominant trait, affecting chromosome 12q23-24.1. It starts at first or second decade of life, it is characterized by cutaneous manifestations due to several hyperkeratotic papules that affect seborrheic areas such as head, neck and thorax. This article seeks to present reports of cases of two patients in a Hospital in Bogotá-Colombia and their relationship with psychiatric illnesses such as bipolar affective disorder and mental retardation. A complete clinical history was made, the patients were examined, and informed consent was signed for taking pictures and using them for educational purposes. With this information, we proceeded to look for bibliography in the most recognized databases such as: Pubmed, Science Direct, Embase using advanced searches with key words, related words like Darier White disease and its relationship with psychiatric illnesses in general. Finally, each of the cases described as Darier's disease was approached with the clinical association of psychiatric illnesses such as bipolar affective disorder and mental retardation, with which this disease shows a close relationship in relation to the percentages of presentation.

Crime sexual e retardo mental / Sexual crime and mental retardation / Délit sexuel et handicap mental / Delito sexual y retraso mental

Apresentamos o caso de um homem que cometeu estupro de menino de cinco anos de idade. A perícia psiquiátrica concluiu que o mesmo apresentava retardo mental moderado, sendo inimputável. Atualmente ele cumpre medida de segurança em Hospital de Custódia e Tratamento Psiquiátrico do Rio de Janeiro. São discutidos fatores motivadores desse comportamento sexual, bem como as questões subjetivas do paciente que contribuíram para esse comportamento.

We present the case of a man who committed rape of a five-year-old boy. The psychiatric expert investigation concluded that he has moderate mental retardation, being not guilty by reason of insanity. He is currently committed into a forensic hospital in Rio de Janeiro. Motivating factors as well as the patient's subjective issues that may have contributed to this sexual behavior are discussed.

Nous présentons le cas d'un homme qui a commis le viol d'un garçon de cinq ans. L'expertise psychiatrique a conclu qu'il présente une arriération mentale modérée, n'étant donc pas criminellement responsable dû à son handicap mental. Il est actuellement interné dans un hôpital de détention préventive et de soins psychiatriques à Rio de Janeiro. Nous discutons les facteurs motivants ainsi que les problèmes subjectifs du patient qui peuvent avoir contribué à ce comportement.

Presentamos el caso de un hombre que abusó sexualmente de un niño de 5 años. El peritaje psiquiátrico del agresor concluyó que, el mismo, presentaba retraso mental moderado, y se le consideró inimputable. Actualmente, cumple la medida de seguridad en el Hospital de Custodia y Tratamiento Psiquiátrico de Río de Janeiro. Se discuten los factores motivadores, así como las cuestiones subjetivas del paciente, cuestiones tales que contribuyeron con este comportamiento sexual.

Dieser Artikel diskutiert den Fall eines Mannes, der einen 5-jährigen Jungen vergewaltigte. Das psychiatrische Gutachten ergab, dass dieser an einer mäßigen geistigen Behinderung leidet und deshalb schuldunfähig ist. Er ist derzeit in Rio de Janeiros Anstalt für Sicherungsverwahrung und psychiatrischer Pflege interniert. Auslösende Faktoren sowie die subjektiven Probleme des Patienten, die möglicherweise zu diesem sexuellen Verhalten beigetragen haben werden analysiert.

Cri-du-chat syndrome diagnosed in a 21-year-old woman by means of comparative genomic hybridization / Síndrome de cri du chat diagnosticado en mujer de 21 años por hibridación genómica comparativa

Abstract The cri-du-chat syndrome is caused by a deletion on the short arm of chromosome number 5. The size of genetic material loss varies from the 5p15.2 region only to the whole arm. Prevalence rates range between 1:15000 and 1:50000 live births. Diagnosis is suspected on infants with a high-pitched (cat-like) cry, facial dysmorfism, hypotonia and delayed psychomotor development. In adults, phenotypic findings are less specific. It is confirmed through high-resolution G-banding karyotype, fluorescent in situ hybridization or microarray-based comparative genomic hybridization (a-CGH). The following is the case report of a 21-year-old female patient with severe mental retardation and trichotillomania, who does not control sphincters and does not bathe or eat by herself. Her communication is based only on sounds and dysmorphic facies. The G-band karyotype reported is 46, XX. a-CGH shows 18.583Mb interstitial microdeletion in 5p15.33p14.3, including the cri-du-chat critical region. In children or adults with unexplained mental retardation and normal karyotype results (like this case), an a-CGH should be performed to make an etiological diagnosis, establish the prognosis, order additional medical tests and specific treatments, and offer appropriate genetic counseling.

Resumen El síndrome de cri du chat o del maullido de gato es causado por una deleción en el brazo corto del cromosoma 5; el tamaño de la pérdida de material genético varía desde solo la región 5p15.2 hasta el brazo entero. La prevalencia va desde 1 por 15 000 habitantes hasta 1 por 50 000 habitantes. Su diagnóstico se puede confirmar con cariotipo con bandas G de alta resolución, hibridación fluorescente in situ o hibridación genómica comparativa por microarreglos (HGCm); este se sospecha en infantes con un llanto similar al maullido de un gato, fascies dismórficas, hipotonía y retardo del desarrollo psicomotor; sin embargo, en los adultos afectados los hallazgos fenotípicos son menos específicos. Se presenta el caso de una mujer de 21 años con retardo mental severo y tricotilomanía, que no controla esfínteres y no se baña ni come sola; solo emite ruidos y tiene facies dismórficas. El cariotipo de bandas G es reportado 46, XX y la HGCm muestra microdeleción de 18.583Mb en 5p15.33p14.3, incluyendo región crítica de cri du chat. En pacientes de este tipo se debe realizar HGCm para hacer un diagnóstico etiológico, establecer un pronóstico, ordenar pruebas médicas adicionales y tratamientos específicos y realizar la adecuada asesoría genética.

De la investigación científica al diseño de políticas de salud: la experiencia con la eliminación de la deficiencia de yodo en Perú / From scientific research to health policy design: the experience of iodine deficiency elimination in Peru

RESUMEN La investigación científica es una función esencial en salud pública; permite reconocer problemas y situaciones que comprometen la salud y la identificación de soluciones. La investigación es esencial para formulación de políticas desalud. Es imperativo para los países tener sistemas nacionales de investigación. Últimamente, ha habido un significativo avance global, pero el crecimiento no es uniforme, las condiciones son escasas en países con ingresos medianos y bajos. Una experiencia que ilustra esta situación ha sido la investigación de la deficiencia de yodo (DI) en Perú y la aplicación de resultados para la creación de un programa de salud pública. La investigación demostró persistente DI, que durante la gestación causa daño cerebral y retardo mental, que el uso de aceite yodado en la prevención y tratamiento tiene efecto inmediato y larga duración, y validó la concentración urinaria del yodo como el mejor indicador de nutrición de yodo. Estos resultados fueron tomados en cuenta por el Ministerio de Salud y en 1983 se creó el Programa Nacional de Control del Bocio y Cretinismo Endémicos, que ha logrado la eliminación virtual de la DI desde 1995.

ABSTRACT Scientific research is an essential public health function, enabling recognition of problems that compromise health and facilitating solutions. Research is essential to formulate health policy at a national level. There has been significant but inconsistent overall progress, due to economic conditions in low- and middle-income countries. An example that illustrates this situation is the investigation of iodine deficiency (ID) in Peru, and the application of the results for development of a public health program. The research demonstrated persistent ID, which causes fetal brain damage and subsequent mental retardation. The use of iodinated oil to prevent and treat ID was shown to have an immediate and long-term effect, and confirmed that urinary concentration of iodine was the best indicator of iodine intake. These results were accepted by the Ministry of Health, and the National Program for the Control of Endemic Goiter and Cretinism was created in 1983, achieving virtual elimination of ID by 1995.

Health profiles in people with intellectual developmental disorders / Perfiles de salud en personas con trastornos del desarrollo intelectual

Abstract: Objective: To better understand the health profiles of people with intellectual disability (ID), focusing on the variables that are associated with a poorer health status. Materials and methods: Data were collected from the Survey on Disability, Personal Autonomy and Dependency (EDAD 2008) of the Spanish National Statistics Institute (INE). The health data of 2840 subjects with IDD were analyzed in order to verify the impact of different variables on their health profiles. Results: People with severe and profound levels of IDD presented a higher number of medical diagnoses. At residence centers there was a larger proportion of individuals with a higher prevalence of chronic diseases and more severe conditions; age also was an important factor. Conclusion: The health profiles of individuals with IDD differ depending on the severity level of their IDD and their degree of institutionalization. Further research is needed to provide better health care for people with IDD.

Resumen: Objetivo: Conocer los perfiles de salud de las personas con discapacidad intelectual (DI), incidiendo en las variables que se relacionan con un peor estado de salud. Material y métodos: Se han empleado datos procedentes de la Encuesta sobre Discapacidades, Autonomía personal y situaciones de Dependencia (EDAD 2008) del Instituto Nacional de Estadística (INE). Se han comparado los datos de salud de 2840 sujetos con discapacidad intelectual para analizar las diferencias en sus perfiles de salud. Resultados: En los centros residenciales hay una mayor proporción de personas con DI profunda y severa, de edad más avanzada y con mayor prevalencia de enfermedades crónicas. Las personas con niveles más graves de DI presentan un mayor número de diagnósticos de enfermedades. Conclusión: Los perfiles de salud de las personas con DI difieren en función de su grado de institucionalización y su nivel de DI. Es necesario seguir investigando para ofrecer una mejor atención sanitaria a las personas con DI.

Nuevas consideraciones sobre la salud de las personas con trastornos del desarrollo intelectual / New considerations on the health of the persons with intellectual developmental disorders

Resumen: La literatura reciente indica que las personas con trastornos del desarrollo intelectual (TDI) presentan diferencias respecto de la población general en cuanto a la prevalencia de determinadas enfermedades y a la atención sanitaria que reciben. El conocimiento actual con base en la evidencia es aún muy escaso en países no anglosajones. Los proyectos europeos POMONA-I y POMONA-II tenían el objetivo de recoger información sobre el estado de salud de las personas con TDI en Europa. Actualmente, el proyecto POMONA-ESP en España pretende recoger dicha información en una muestra amplia y representativa de personas con TDI. También se están llevando a cabo otros estudios sobre la necesidad de contar con servicios especializados y sobre la formación que reciben los profesionales sanitarios sobre TDI. En este artículo se revisan las últimas evidencias sobre la salud de las personas con TDI y se exponen las principales actividades de investigación y asistencia sanitaria sobre este tema.

Abstract: Recent literature indicates that people with Disorders of Intellectual Development (DID) experience health disparities in the pathologies that they present, and a worst access to health care. However, current evidence-based knowledge is still sparse outside the Anglo-Saxon countries. The POMONA-I and POMONA-II European projects aimed to collect information on the health status of people with DID in Europe. The POMONA-ESP project in Spain is meant to collect health information in a wide and representative sample of persons with DID. Also, there are studies that claim for the need of specialized services for people with DID at the public health system. There are also studies about the current state of the education and training about DID for students within the health sector. In this paper we review the latest evidences about the health of the persons with DID and we present the main research activities and care initiatives about this issue.

Etapas históricas del proceso de orientación a la familia del niño discapacitado en Cuba / Historical periods of the guidance process of handicap child family in Cuba

El devenir histórico concreto del proceso de orientación familiar hace posible escalar distintos niveles de satisfacción en cuanto a la atención de las necesidades de los padres. De la importancia que tradicionalmente se le concede a la familia en el desarrollo integral de sus hijos, se deriva la utilidad de su adecuada preparación. A tales efectos se realizó el presente estudio con el objetivo describir las etapas del proceso de orientación a la familia para la formación ciudadana de los niños con retraso mental, lo cual permitió llegar a importantes conclusiones.

The concrete historical evolution of the family guidance process makes possible climbing different satisfaction levels as for paying attention to the parents necessities. The importance that is given to the family in the integral development of their children, results in the usefulness of its adequate preparation. To such effects, this study was carried out with the purpose of describing the stages of the family guidance process for the citizen training of children with mental retardation, which allowed to reach important conclusions

Clinical, molecular, and pharmacological aspects of FMR1 related disorders. / Aspectos clínicos, moleculares y farmacológicos en los trastornos asociados a gen 1 del retraso mental del X frágil.

BACKGROUND: Fragile X syndrome, the most common inherited cause of intellectual disability, is associated with a broad spectrum of disorders across different generations of a single family. This study reviews the clinical manifestations of fragile X-associated disorders as well as the spectrum of mutations of the fragile X mental retardation 1 gene (FMR1) and the neurobiology of the fragile X mental retardation protein (FMRP), and also provides an overview of the potential therapeutic targets and genetic counselling. DEVELOPMENT: This disorder is caused by expansion of the CGG repeat (>200 repeats) in the 5 prime untranslated region of FMR1, resulting in a deficit or absence of FMRP. FMRP is an RNA-binding protein that regulates the translation of several genes that are important in synaptic plasticity and dendritic maturation. It is believed that CGG repeat expansions in the premutation range (55 to 200 repeats) elicit an increase in mRNA levels of FMR1, which may cause neuronal toxicity. These changes manifest clinically as developmental problems such as autism and learning disabilities as well as neurodegenerative diseases including fragile X-associated tremor/ataxia syndrome (FXTAS). CONCLUSIONS: Advances in identifying the molecular basis of fragile X syndrome may help us understand the causes of neuropsychiatric disorders, and they will probably contribute to development of new and specific treatments.