Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes.

Interferon regulatory factor 6 (IRF6) belongs to a family of nine transcription factors that share a highly conserved helix-turn-helix DNA-binding domain and a less conserved protein-binding domain. Most IRFs regulate the expression of interferon-alpha and -beta after viral infection, but the function of IRF6 is unknown. The gene encoding IRF6 is located in the critical region for the Van der Woude syndrome (VWS; OMIM 119300) locus at chromosome 1q32-q41 (refs 2,3). The disorder is an autosomal dominant form of cleft lip and palate with lip pits, and is the most common syndromic form of cleft lip or palate. Popliteal pterygium syndrome (PPS; OMIM 119500) is a disorder with a similar orofacial phenotype that also includes skin and genital anomalies. Phenotypic overlap and linkage data suggest that these two disorders are allelic. We found a nonsense mutation in IRF6 in the affected twin of a pair of monozygotic twins who were discordant for VWS. Subsequently, we identified mutations in IRF6 in 45 additional unrelated families affected with VWS and distinct mutations in 13 families affected with PPS. Expression analyses showed high levels of Irf6 mRNA along the medial edge of the fusing palate, tooth buds, hair follicles, genitalia and skin. Our observations demonstrate that haploinsufficiency of IRF6 disrupts orofacial development and are consistent with dominant-negative mutations disturbing development of the skin and genitalia.

Critical periods in the variation in body composition in school children.

OBJECTIVE: To identify critical periods in the variation in body composition during a school year and determine possible causes. METHODS: A total of 363 boys and girls aged between 10 and 14 years participated in the study. Before and after the Winter Holidays (WIH) and National Holidays (NAH) (July and September, respectively), measurements were taken of body weight, body fat percentage, waist perimeter, time spent on physical activity and hours of sleep in order to determine the variations. The normality of the data was confirmed and the means were compared with an alpha significance level of p<0.05. RESULTS: The school children increased in weight by 600 g and 510 g in the NAH and WIH, respectively (p<0.0001), and their body fat percentage was significantly increased during both periods (0.51%); however, the waist perimeter measurement saw no significant changes. It can also be seen that in NAH physical activity dropped by an important amount (-41 min, p<0.0001), though this did not occur in WIH. A significant increase in hours of sleep was also seen during the two holiday periods (~1 to 2 hours/day). CONCLUSION: It is concluded that both NAH and WIH can be considered critical periods due to the sharp increase in body weight and body fat percentage in the school children, where a possible cause is the reduction in time spent on physical activity.

Objetivo: Identificar periodos críticos en la variación de la composición corporal durante un año escolar y determinar causas posibles. Métodos: Un total de 363 niños y niñas entre 10 y 14 años participaron en el estudio. Antes y después de las Vacaciones de invierno (VI) y Vacaciones nacionales (VN) (julio y septiembre, respectivamente), se tomaron mediciones de peso corporal, porcentaje de grasa corporal, perímetro en la cintura, tiempo dedicado a actividad física y horas de sueño para determinar las variaciones. La normalidad de los datos fue confirmada y las medias fueron comparadas con un nivel de significancia alfa de p.

Meta-analysis of 13 genome scans reveals multiple cleft lip/palate genes with novel loci on 9q21 and 2q32-35.

Isolated or nonsyndromic cleft lip with or without cleft palate (CL/P) is a common birth defect with a complex etiology. A 10-cM genome scan of 388 extended multiplex families with CL/P from seven diverse populations (2,551 genotyped individuals) revealed CL/P genes in six chromosomal regions, including a novel region at 9q21 (heterogeneity LOD score [HLOD]=6.6). In addition, meta-analyses with the addition of results from 186 more families (six populations; 1,033 genotyped individuals) showed genomewide significance for 10 more regions, including another novel region at 2q32-35 (P=.0004). These are the first genomewide significant linkage results ever reported for CL/P, and they represent an unprecedented demonstration of the power of linkage analysis to detect multiple genes simultaneously for a complex disorder.

Evaluación epidemiológica genética de labio bendido con o sin paladar bendido en genealogías extendidas multigeneracionales pesquisadas en Colombia

Objetivo: discriminar los componentes genéticos y ambientales involucrados en generar la susceptibilidadpara labio hendido con o sin paladar hendido (LH+PH)en familias de Antioquia, Colombia y buscar asociación o ligamiento a marcadores genéticos. Material y método: se seleccionaron 60 individuos afectados de LH+PH y se reconstruyó su genealogía. Al tiempo, se seleccionaron 80 individuos apareados por edad, sexo y condición socioeconómica que sirvieron como controles. Se realizaron análisis de segregación simple, cálculos de heredabilidad, prueba de hipótesis sobre las prediciones del modelo multifactorial y análisis de asociaciones y ligamiento genético. Resultados: el análisis de segregación simple mostró un mejor ajuste del modelo de locus mayor recesivo con penetrancia incompleta. La heredabilidad de 96 por ciento está de acuerdo con la existencia de un gen mayor. Las pruebas de hipótesis refutaron el modelo de herencia multifactorial. La frecuencia del gen mayor que induce la susceptibilidad para desarrollar LH+PH fue de 0,037. Se encontró covarianza significante entre el fenotipo LH+PH y el genotipo JKa/JKa (grupo sanguíneo Kidd p<0,01, riesgo relativo =0,2). A partir de este se practicó análisis secuencial de ligamiento entre LH+PH y dicho marcador en una familia extendida multigeneracional que no mostró resultados concluyentes. Conclusiones: los hallazgos sugieren que los efectos ambientales son mínimos en la susceptibilidad a desarrollar LH+PH y es más importante el efecto de un gen mayor