Biogeographical origin and timing of the founder ichthyosis TGM1 c.1187G > A mutation in an isolated Ecuadorian population

An unusually high frequency of the lamellar ichthyosis TGM1 mutation, c.1187G > A, has been observed in the Ecuadorian province of Manabi. 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 Manabi. 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 Manabi could have favored a founder effect that explains the high prevalence of TGM1 c.1187G > A in this region

Validación del método de cuantificación del área corporal afectada por la psoriasis mediante lápiz óptico

Introducción: La determinación de la superficie corporal afectada, Body Surface Area (BSA), es una de las escalas de medida más empleadas en la evaluación de la gravedad de la psoriasis, pero no está exenta de inconvenientes. Objetivo: Validación de un nuevo sistema de medida del BSA. Material y método: Estudio multicéntrico, prospectivo, que incluyó 56 pacientes con psoriasis. Cada paciente fue evaluado en 2 visitas por 2 dermatólogos del mismo Centro que valoraron BSA mediante 2 procedimientos: método visual «tradicional» (MT), palma mano = 1%; y el método «lápiz óptico» (LO), lápiz capacitivo puntero sobre pantalla táctil con medición de la superficie mediante software específico. Resultados: Se observó una concordancia aceptable entre ambos métodos, con coeficiente de correlación intraclase (CCI) de 0,87, pero con unos límites de acuerdo excesivamente grandes y un sesgo sistemático consistente en mayores medidas de BSA con MT que con LO. La concordancia entre métodos fue superior en el tronco y las extremidades inferiores (CCI > 0,8). La fiabilidad intraobservador fue excelente con ambos métodos (CCI: MT, 0,97; LO, 0,98). La fiabilidad interobservador fue elevada (CCI: MT, 0,91; LO, 0,94), pero el BSA medio difirió significativamente entre observadores. Además, el CCI se redujo drásticamente cuando se consideró la cabeza exclusivamente. Conclusiones: El presente estudio valida el método LO para la medición de la superficie corporal afectada en pacientes con psoriasis. Muestra una buena concordancia con el MT, presentando menos variabilidad y mayor fiabilidad interobservador

Multiple Local and Recent Founder Effects of TGM1 in Spanish Families

<div><h3>Background</h3><p>Mutations in the <em>TGM1</em> gene encoding transglutaminase 1 are a major cause of autosomal recessive congenital ichthyosis. In the Galician (NW Spain) population, three mutations, c.2278C>T, c.1223_1227delACAC and c.984+1G>A, were observed at high frequency, representing ∼46%, ∼21% and ∼13% of all <em>TGM1</em> gene mutations, respectively. Moreover, these mutations were reported only once outside of Galicia, pointing to the existence of historical episodes of local severe genetic drift in this region.</p> <h3>Methodology/Principal Findings</h3><p>In order to determine whether these mutations were inherited from a common ancestor in the Galician population, and to estimate the number of generations since their initial appearance, we carried out a haplotype-based analysis by way of genotyping 21 SNPs within and flanking the <em>TGM1</em> gene and 10 flanking polymorphic microsatellite markers spanning a region of 12 Mb. Two linkage disequilibrium based methods were used to estimate the time to the most recent common ancestor (TMRCA), while a Bayesian-based procedure was used to estimate the age of the two mutations. Haplotype reconstruction from unphased genotypes of all members of the affected pedigrees indicated that all carriers for each of the two mutations harbored the same haplotypes, indicating common ancestry.</p> <h3>Conclusions/Significance</h3><p>In good agreement with the documentation record and the census, both mutations arose between 2,800–2,900 years ago (y.a.), but their TMRCA was in the range 600–1,290 y.a., pointing to the existence of historical bottlenecks in the region followed by population growth. This demographic scenario finds further support on a Bayesian Coalescent Analysis based on <em>TGM1</em> haplotypes that allowed estimating the occurrence of a dramatic reduction of effective population size around 900–4,500 y.a. (95% highest posterior density) followed by exponential growth.</p> </div