Ancient origin of the CAG expansion causing Huntington disease in a Spanish population

25 p. Figuras, tablas, bibliografíaHuntington disease (HD, MIM# 143100) is an autosomal dominant neurodegenerative disorder characterized clinically by progressive motor impairment, cognitive decline, and emotional deterioration. The disease is caused by the abnormal expansion of a CAG trinucleotide repeat in the first exon of the huntingtin gene in chromosome 4p16.3. HD is spread worldwide and it is generally accepted that few mutational events account for the origin of the pathogenic CAG expansion in most populations. We have investigated the genetic history of HD mutation in 83 family probands from the Land of Valencia, Eastern Spain. An analysis of the HD/CCG repeat in informative families suggested that at least two main chromosomes were associated in the Valencian population, one associated with allele 7 (77 mutant chromosomes) and one associated with allele 10 (2 mutant chromosomes). Haplotype A-7-A (H1) was observed in 47 out of 48 phase-known mutant chromosomes, obtained by segregation analysis, through the haplotype analysis of rs1313770-HD/CCGrs82334, as it also was in 120 out of 166 chromosomes constructed by means of the PHASE program. The genetic history and geographical distribution of the main haplotype H1 were both studied by constructing extended haplotypes with flanking STRs D4S106 and D4S3034. We found that we were able to determine the age of the CAG expansion associated with the haplotype H1 as being between 4,700 and 10,000 years ago. Furthermore, we observed a nonhomogenous distribution in the different regions associated with the different extended haplotypes of the ancestral haplotype H1, suggesting that local founder effects have occurred.This work was supported by the Fondo de investigación Sanitaria (FIS grant 01/1159), the Instituto de Salud Carlos III (grant G03/56) for the Spanish Network on Cerebellar Ataxias, and the Generalitat Valenciana (grant GRUPOS03/015).Peer reviewe

Ancient origin of the CAG expansion causing Huntingtons disease in a Spanish population.

[EN] Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterized clinically by progressive motor impairment, cognitive decline, and emotional deterioration. The disease is caused by the abnormal expansion of a CAG trinucleotide repeat in the first exon of the huntingtin gene in chromosome 4p16.3. HD is spread worldwide and it is generally accepted that few mutational events account for the origin of the pathogenic CAG expansion in most populations. We have investigated the genetic history of HD mutation in 83 family probands from the Land of Valencia, in Eastern Spain. An analysis of the HD/CCG repeat in informative families suggested that at least two main chromosomes were associated in the Valencian population, one associated with allele 7 (77 mutant chromosomes) and one associated with allele 10 (two mutant chromosomes). Haplotype A-7-A (H1) was observed in 47 out of 48 phase-known mutant chromosomes, obtained by segregation analysis, through the haplotype analysis of rs1313770-HD/CCG-rs82334, as it also was in 120 out of 166 chromosomes constructed by means of the PHASE program. The genetic history and geographical distribution of the main haplotype H1 were both studied by constructing extended haplotypes with flanking short tandem repeats (STRs) D4S106 and D4S3034. We found that we were able to determine the age of the CAG expansion associated with the haplotype H1 as being between 4,700 and 10,000 years ago. Furthermore, we observed a nonhomogenous distribution in the different regions associated with the different extended haplotypes of the ancestral haplotype H1, suggesting that local founder effects have occurred.We are grateful for the kind collaboration of patients and families. This work was supported by the Fondo de investigación Sanitaria (FIS grant 01/1159), the Instituto de Salud Carlos III (grant G03/56) for the Spanish Network on Cerebellar Ataxias, and the Generalitat Valenciana (grant GRUPOS03/015).García-Planells, J.; Burguera, JA.; Solís, P.; Millán, JM.; Ginestar Peiro, D.; Palau, F.; Espinós-Armero, CÁ. (2005). Ancient origin of the CAG expansion causing Huntingtons disease in a Spanish population. Human Mutation. 25(5):453-459. https://doi.org/10.1002/humu.2016745345925

Enfermedades neurológicas hereditarias: genes, mutaciones, clínica y epidemiologia genética (premio Reina Sofía 2004, de prevención de deficiencias)

Esta memoria quiere ser un resumen de los estudios y hallazgos de laboratorio y de las contribuciones científicas de la Unidad de Genética Molecular en el campo de la genética molecular de las enfermedades neurológicas, trastornos que se encuadran en el término de enfermedades raras, así como las aplicaciones en medicina clínica a las que han dado lugar, concretamente por lo que respecta al diagnóstico molecular y al consejo genético. La memoria está dividida en cuatro capítulos que hacen referencia a las ataxias hereditarias, las neuropatías periféricas hereditarias, los trastornos del movimiento y las distrofias musculares. En todos ellos se mencionan explícitamente los aspectos clínicos del diagnóstico molecular, incluidos los diagnósticos prenatal y presintomático, así como el consejo genético

The pharmacist in the administration of the autonomous community of Andalusia

Objetivo: En primer lugar determinar las condiciones de acceso al Cuerpo de Farmacéuticos adscrito a la Administración Sanitaria de la Junta de Andalucía y en segundo lugar, conocer las distintas modalidades, cómo se han organizado los distintos cuerpos y cómo se estructuran en sus diferentes subgrupos. Además se analiza y define su régimen laboral. En tercer lugar, determinar la estructura orgánica y funciones de los distintos Cuerpos a los que tiene acceso el farmacéutico en la Administración de la Comunidad Autónoma Andaluza Metodología: Revisión de la normativa, vigente y derogada, que regula los cuerpos y el sistema de acceso para Farmacéutico en la Comunidad Autónoma Andaluza. Conclusión: La figura del farmacéutico como agente sanitario en la legislación autonómica andaluza, se encuentra regulada en distintas normas que exigen una interpretación de acuerdo a los criterios de la Ley 6/185 de Ordenación de la Función Pública de la Junta de Andalucía. Las distintas modalidades de ejercicio profesional, ya sea como agente sanitario de la autoridad autonómica o como profesional especializado se definen en distintos estatutos orgánicos necesarios para definir claramente sus funciones y responsabilidades.Objetive: First to determine the conditions of access to the Pharmacists' Body assigned to the Sanitary Administration of the Meeting of Andalusia and secondly, to know the different modalities, how the different bodies have been organized and how they are structured in his different subgroups. In addition his labor regime is analyzed and defines. Thirdly, to determine the organic structure and functions of the different Bodies to which the pharmacist has access in the Administration of the Autonomous Andalusian Community Methodology: Review of the regulation, in force and repealed, that regulates the bodies and the system of access for Pharmacist in the Autonomous Andalusian Community. Conclusion / discussion The figure of the pharmacist like sanitary agent in the autonomous Andalusian legislation, is regulated in different procedure that demand an interpretation of agreement to the criteria of the Law 6/185 of Arrangement of the Public Function of the Meeting of Andalusia. The different modalities of professional exercise, already be like a sanitary agent of the autonomous authority or as specialized professional they are defined in different organic necessary bylaws to define clearly his functions and responsibilities

Recomendaciones de buenas prácticas para el diagnóstico genético de la distrofia miotónica

Grupo AEGH/CIBERER compuesto por los firmantes anteriores y MJ Trujillo (Instituto de Investigación Sanitaria- Fundación Jiménez Díaz (IIS_FJD); Madrid), P Gallano (Hospital de la Santa Creu i Sant Pau. Barcelona), M Baiget (Hospital de la Santa Creu i Sant Pau. Barcelona), E Grau (Hospital La Fe. Valencia), JM Millan (Hospital La Fe. Valencia), I Marcos (Hospital Virgen del Rocío. Sevilla), Gallego J (Instituto de Investigación Sanitaria- Fundación Jiménez Díaz (IIS_FJD), Madrid) y C Ayuso (Instituto de Investigación Sanitaria- Fundación Jiménez Díaz (IIS_FJD); Madrid y Representante de la AEGH en EMQN).Peer Reviewe

Ancient origin of the CAG expansion causing Huntington disease in a Spanish population

25 p. Figuras, tablas, bibliografíaHuntington disease (HD, MIM# 143100) is an autosomal dominant neurodegenerative disorder characterized clinically by progressive motor impairment, cognitive decline, and emotional deterioration. The disease is caused by the abnormal expansion of a CAG trinucleotide repeat in the first exon of the huntingtin gene in chromosome 4p16.3. HD is spread worldwide and it is generally accepted that few mutational events account for the origin of the pathogenic CAG expansion in most populations. We have investigated the genetic history of HD mutation in 83 family probands from the Land of Valencia, Eastern Spain. An analysis of the HD/CCG repeat in informative families suggested that at least two main chromosomes were associated in the Valencian population, one associated with allele 7 (77 mutant chromosomes) and one associated with allele 10 (2 mutant chromosomes). Haplotype A-7-A (H1) was observed in 47 out of 48 phase-known mutant chromosomes, obtained by segregation analysis, through the haplotype analysis of rs1313770-HD/CCGrs82334, as it also was in 120 out of 166 chromosomes constructed by means of the PHASE program. The genetic history and geographical distribution of the main haplotype H1 were both studied by constructing extended haplotypes with flanking STRs D4S106 and D4S3034. We found that we were able to determine the age of the CAG expansion associated with the haplotype H1 as being between 4,700 and 10,000 years ago. Furthermore, we observed a nonhomogenous distribution in the different regions associated with the different extended haplotypes of the ancestral haplotype H1, suggesting that local founder effects have occurred.This work was supported by the Fondo de investigación Sanitaria (FIS grant 01/1159), the Instituto de Salud Carlos III (grant G03/56) for the Spanish Network on Cerebellar Ataxias, and the Generalitat Valenciana (grant GRUPOS03/015).Peer reviewe

Cribado y diagnóstico prenatal de anomalías genéticas: recomendaciones de consenso SEGO, SEQCML, AEDP

El objetivo de este trabajo es difundir las recomendaciones del consenso entre las sociedades científicas SEGO, SEQCML y AEDP sobre cribado y diagnóstico prenatal de anomalías genéticas, así como una propuesta de indicadores de evaluación, desde una perspectiva de mejora de cada uno de los procesos que constituyen el campo de aplicación de las estrategias actuales de cribado: bioquímico, ecográfico y genético. Asimismo, se recogen recomendaciones relacionadas con los procesos invasivos de diagnóstico prenatal, incluyendo tanto las técnicas de recogida de muestra como las aplicables a su posterior análisis genético. Perspectiva: Se propone unificar criterios e indicadores a nivel nacional, con evaluaciones periódicas. Asimismo, sería muy recomendable establecer una estrategia de cribado prenatal a nivel nacional, dotada con recursos que aseguren la auditoría periódica de dichos indicadores y de los procedimientos diagnósticos, con supervisión por las administraciones sanitarias. Los protocolos deberían ser revisados periódicamente para adaptarse a nuevas tecnologías coste-efectivas

Prenatal screening and diagnosis of genetic abnormalities: SEGO, SEQCML, AEDP consensus recommendations

In this paper, the scientific societies SEGO, SEQCML and AEDP provide a series of consensus-based recommendations for prenatal screening and diagnosis of genetic abnormalities. A set of evaluation indicators are also proposed as a means to improve the quality of the biochemical, ultrasound, and genetic processes involved in prenatal screening and diagnosis of genetic anomalies. Some recommendations are also proposed in relation to invasive prenatal diagnostic procedures, more specifically regarding sample collection and genetic testing. The purpose of this proposal is to unify performance criteria and quality indicators at national level, with audits performed on a regular basis. It is strongly recommended that a national prenatal screening strategy be established and provided with the resources necessary to evaluate the performance of quality indicators and diagnostic procedures under the supervision of health authorities. Protocols should be revised on a regular basis to consider the incorporation of new cost-effective technologies