RESUMO
Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89 985 individuals across 10 sites, including 64 114 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3' terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the NDD subjects (P = 0.002) compared with 44 085 population-based controls. Frequent phenotypes observed in individuals with such deletions include autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), speech delay, anxiety and obsessive compulsive disorder (OCD). The 3'-terminal ASTN2 deletions were significantly enriched compared with controls in males with NDDs, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin near the 3' end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtornos Globais do Desenvolvimento Infantil/genética , Glicoproteínas/genética , Proteínas do Tecido Nervoso/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Cromossomos Humanos Par 9 , Variações do Número de Cópias de DNA , Éxons , Feminino , Expressão Gênica , Estudos de Associação Genética , Predisposição Genética para Doença , Glicoproteínas/metabolismo , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas do Tecido Nervoso/metabolismo , Especificidade de Órgãos , Fenótipo , Polimorfismo de Nucleotídeo Único , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Fatores de Risco , Deleção de Sequência , Fatores de Transcrição/metabolismo , Sítio de Iniciação de Transcrição , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases , Adulto JovemRESUMO
In this study, we examined the sexual communication needs of African-American parents and their adolescent children in relation to faith-based HIV prevention. Eight focus groups of 10 members each were conducted, four with parents and four with adolescents. The sessions were audiotaped and transcribed verbatim. Findings indicated that some African Americans are not knowledgeable about sexually transmitted infections. The sample members were not in agreement about when sexual communications should begin, yet the majority felt that the church was the best place to have these discussions. Healthcare professionals can use the findings from this study to assist faith-based organizations to strengthen the sexual communication skills of African-American families.
Assuntos
Negro ou Afro-Americano , Cristianismo , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Educação Sexual , Adolescente , Adulto , Criança , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Pais , Estados UnidosRESUMO
PURPOSE: This study examined African American adolescents' perceptions of a mobile cell phone (MCP)-enhanced intervention and development of an MCP-based HIV prevention intervention. DESIGN AND METHODS: One focus group was conducted with 11 adolescents who participated in the Becoming a Responsible Teen Text Messaging project. RESULTS: Adolescents said they benefited from the MCP-enhanced approach and were receptive to the idea of developing an MCP-based intervention. PRACTICE IMPLICATIONS: Nurses can use the findings of this report as a starting point in examining the development of MCP-based sexuality education with parents and adolescents.
