A genetic study of autism in Costa Rica: multiple variables affecting IQ scores observed in a preliminary sample of autistic cases

BACKGROUND: Autism is a heritable developmental disorder of communication and socialization that has not been well studied in Hispanic populations. Therefore, we are collecting and evaluating all possible cases of autism from a population isolate in the Central Valley of Costa Rica (CVCR) for a clinical and genetic study. METHODS: We are assessing all subjects and parents, as appropriate, using the newly translated Spanish versions of the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) as well as tests of intelligence and adaptive behavior. Detailed obstetric and family medical/psychiatric histories are taken. All cases are tested for Fragile X and will be extensively evaluated for cytogenetic abnormalities. RESULTS: To date we have obtained clinical evaluations on over 76 cases of possible autism referred to our study and report data for the initial 35 complete cases. The mean age of the probands is 6.7 years, and 31 of the 35 cases are male. Twenty-one of the cases have IQs <50 and only 6 cases have IQs ≥ 70. Over half of the mothers had complications during pregnancy and/or delivery. No cases have tested positively for Fragile X or PKU. Chromosomal G-banding is not yet complete for all cases. CONCLUSION: Diagnostic data gathered on cases of autism in the CVCR using Spanish versions of the ADI-R and ADOS look similar to that generated by studies of English-speaking cases. However, only 17% of our cases have IQs within the normal range, compared to the figure of 25% seen in most studies. This result reflects an ascertainment bias in that only severe cases of autism come to treatment in the CVCR because there are no government-sponsored support programs or early intervention programs providing an incentive to diagnose autism. The severity of mental retardation seen in most of our cases may also be exaggerated by the lack of early intervention programs and the use of IQ tests without Costa Rican norms. Still, we must formally train healthcare providers and teachers to recognize and refer autistic cases with normal or near normal IQs that are not seen in treatment

Alelos intermedios y expandidos en el gen FMR1 en una población con autismo de Costa Rica

Objective: We aimed to determine the distribution of intermediate and expanded FMR1 alleles in Costa Rican individuals diagnosed with autism. Materials and methods: A total of 212 autism spectrum disorder (ASD) cases of Costa Rican individuals and 943 male newborn controls were screened by means of polymerase chain reaction to determine the frequency of intermediate, premutation, and full mutation FMR1 alleles. Full mutation suspected cases were confirmed by Southern blot analyses. Frequencies of FMR1 alleles in the case group were compared with frequencies observed in a population-based sample of male newborn controls. Results: A significant excess of intermediate allele carriers was found in ASD individuals as compared to controls (χ2 test, p < 0.001). Four, out of 188 males in the case group, were identified as full mutation carriers. Conclusions: Our results suggest a possible involvement of the gray zone or intermediate alleles in ASD.Objetivo: Determinar la distribución de los alelos FMR1 intermedios y expandidos en individuos costarricenses diagnosticados con autismo. Materiales y métodos: Para determinar la frecuencia de la mutación intermedia, la premutación y la mutación completa en el gen FMR1, se tamizaron 212 casos con autismo y 943 recién nacidos de sexo masculino como controles. Los casos con sospecha de ser portadores de la mutación completa se confirmaron mediante análisis de transferencia de Southern. Las frecuencias de los alelos del gen FMR1 en el grupo de casos se compararon con las frecuencias observadas en una muestra basada en la población de controles de recién nacidos varones. Resultados: Se encontró un exceso significativo de portadores de alelos intermedios en los individuos con autismo en comparación con los controles (χ2, p < 0.001). Cuatro varones del grupo de casos fueron identificados como portadores de la mutación completa. Conclusiones: Nuestros resultados sugieren una posible participación de los alelos intermedios en el autismo.Consejo Nacional de Investigaciones Científicas y Tecnológicas/[]/CONICIT/Costa RicaUniversidad de Costa Rica/[742-A3-303]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA