RESUMEN
An unusually high frequency of the lamellar ichthyosis TGM1 mutation, c.1187G > A, has been observed in the Ecuadorian province of Manabí. Recently, the same mutation has been detected in a Galician patient (Northwest of Spain). By analyzing patterns of genetic variation around this mutation in Ecuadorian patients and population matched controls, we were able to estimate the age of c.1187G > A and the time to their most recent common ancestor (TMRCA) of c.1187G > A Ecuadorian carriers. While the estimated mutation age is 41 generations ago (~1,025 years ago [ya]), the TMRCA of Ecuadorian c.1187G > A carrier haplotypes dates to just 17 generations (~425 ya). Probabilistic-based inferences of local ancestry allowed us to infer a most likely European origin of a few (16% to 30%) Ecuadorian haplotypes carrying this mutation. In addition, inferences on demographic historical changes based on c.1187G > A Ecuadorian carrier haplotypes estimated an exponential population growth starting ~20 generations, compatible with a recent founder effect occurring in Manabí. Two main hypotheses can be considered for the origin of c.1187G > A: (i) the mutation could have arisen in Spain >1,000 ya (being Galicia the possible homeland) and then carried to Ecuador by Spaniards in colonial times ~400 ya, and (ii) two independent mutational events originated this mutation in Ecuador and Galicia. The geographic and cultural characteristics of Manabí could have favored a founder effect that explains the high prevalence of TGM1 c.1187G > A in this region.
Asunto(s)
Ictiosis Lamelar/patología , Transglutaminasas/genética , Ecuador , Genotipo , Haplotipos , Humanos , Ictiosis Lamelar/genética , Polimorfismo de Nucleótido Simple , Análisis de Componente Principal , Secuencias Repetidas en Tándem/genéticaAsunto(s)
Ictiosis/genética , Lipasa/genética , Mutación Missense/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Heterocigoto , Homocigoto , Humanos , Lactante , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Adulto JovenAsunto(s)
Ictiosis Lamelar/genética , Lipasa/genética , Mutación Missense/genética , Adolescente , Adulto , Femenino , Heterocigoto , Homocigoto , Humanos , MasculinoRESUMEN
No disponible
Asunto(s)
Humanos , Femenino , Neoplasias de la Mama/epidemiología , Genes BRCA1 , Genes BRCA2 , Reacción en Cadena de la Polimerasa Multiplex , Mutación , Prevalencia , España/epidemiología , Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad , Proteínas Serina-Treonina Quinasas/genéticaAsunto(s)
Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad , Proteínas Serina-Treonina Quinasas/genética , Neoplasias de la Mama/epidemiología , Quinasa de Punto de Control 2 , Femenino , Genes BRCA1 , Genes BRCA2 , Humanos , Reacción en Cadena de la Polimerasa Multiplex , Mutación , Prevalencia , España/epidemiologíaRESUMEN
BACKGROUND: Mutations in six genes have been identified in autosomal recessive congenital ichthyosis (ARCI). To date, few studies have analysed the spectrum of these mutations in specific populations. OBJECTIVES: We have studied the characteristics of patients with ARCI in Galicia (NW Spain). Methods We recruited patients by contacting all dermatology departments of Galicia and the Spanish patient organization for ichthyosis. TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 were analysed in the patients and their relatives. RESULTS: We identified 23 patients with ARCI and estimated a prevalence of 1 : 122 000. Twenty of the patients were studied. Seventeen of them were clinically categorized as having lamellar ichthyosis (LI) and three as having congenital ichthyosiform erythroderma (CIE). TGM1 and ALOXE3 mutations were identified in 12/16 (75%) probands whereas no ALOX12B, NIPAL4 and CYP4F22 mutations were found. TGM1 mutations were found in 11/13 (85%) of LI probands. ALOXE3 mutations were identified in a single patient with CIE. Remarkably, mutations p.Arg760X, p.Asp408ValfsX21 and c.984+1G>A of TGM1 were present in six, four and two families, accounting for 41%, 23% and 14% of all TGM1 mutant alleles, respectively. CONCLUSIONS: The high percentage of patients with the same TGM1 mutations, together with the high number of homozygous probands (64%), indicates the existence of a strong founder effect in our population.
Asunto(s)
Efecto Fundador , Eritrodermia Ictiosiforme Congénita/genética , Mutación/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Araquidonato 12-Lipooxigenasa/genética , Niño , Preescolar , Sistema Enzimático del Citocromo P-450/genética , Femenino , Genotipo , Homocigoto , Humanos , Eritrodermia Ictiosiforme Congénita/etnología , Lipooxigenasa/genética , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Receptores de Superficie Celular/genética , España/etnología , Transglutaminasas/genéticaRESUMEN
Biallelic inactivation of ATM gene causes the rare autosomal recessive disorder Ataxia-telangiectasia (A-T). Female relatives of A-T patients have a two-fold higher risk of developing breast cancer (BC) compared with the general population. ATM mutation carrier identification is laborious and expensive, therefore, a more rapid and directed strategy for ATM mutation profiling is needed. We designed a case-control study to determine the prevalence of 32 known ATM mutations causing A-T in Spanish population in 323 BRCA1/BRCA2 negative hereditary breast cancer (HBC) cases and 625 matched Spanish controls. For the detection of the 32 ATM mutations we used the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technique. We identified one patient carrier of the c.8264_8268delATAAG ATM mutation. This mutation was not found in the 625 controls. These results suggest a low frequency of these 32 A-T causing mutations in the HBC cases in our population. Further case-control studies analyzing the entire coding and flanking sequences of the ATM gene are warranted in Spanish BC patients to know its implication in BC predisposition.
Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Proteínas de Ciclo Celular/genética , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Supresoras de Tumor/genética , Proteínas de la Ataxia Telangiectasia Mutada , Estudios de Casos y Controles , ADN/análisis , ADN/genética , Análisis Mutacional de ADN , Familia , Femenino , Pruebas Genéticas , Humanos , Masculino , Pronóstico , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
En estos últimos años hemos asistido al enorme desarrollo de la genómica y sus aplicaciones en diversos campos de la biomedicina. Esto ha sido en gran parte posible gracias al gran empuje tecnológico que han experimentado las nuevas técnicas de genotipado y de ultra secuenciación. Sin duda, el estudio de la enfermedad compleja ha sido uno de los grandes beneficiados de este gran desarrollo. Asimismo, existen muchas enfermedades pediátricas que pueden abordarse siguiendo las estrategias que, hoy por hoy, se emplean en la genómica de la enfermedad multifactorial. Esta revisión pretende acercar a la pediatría las posibilidades que ofrece la genómica de hoy en día en este campo. Para ello, se discuten los distintos modelos de estudios, así como los problemas que a menudo surgen cuando los diseños experimentales son deficientes (AU)
The last few years have experienced an important growth of genomics and its different applications in biomedicine. In part, this has been possible due to the sudden development of the new genotyping technology and ultra-sequencing. The study of the genetic basis of the complex disease has been the main beneficiary of such technological development. There are a good number of pediatric diseases that can be approached following the same strategies employed in the genomic study of the multi-factorial disease. Thus, the present article aims to review the different applications of genomics to Pediatrics as well as to discuss the different strategies available and the preventions needed to avoid false positive associations (AU)