RESUMO
Duplications of chromosome 15 may be one of the most common single genetic causes of autism spectrum disorders (ASD), aside from fragile X. Most of the cases are associated with maternally derived interstitial duplication involving 15q11-13. This case report describes a female proband with a maternally derived interstitial duplication of proximal 15q. She did not exhibit any symptoms of ASD apart from some developmental delay. By adolescence, she showed mild dysmorphism, a discrepant profile on the Wechsler Intelligence Scale for Children (Verbal IQ = 87; Performance IQ = 65) and a major deficit in visual-spatial abilities affecting fine motor skills, mathematical reasoning, visual memory and some global reading tasks. This is one of the first reports of a child with a maternal duplication who exhibits a visual-spatial deficit without ASD.
Assuntos
Transtorno Autístico/genética , Cromossomos Humanos Par 15/genética , Duplicação Gênica , Orientação , Reconhecimento Visual de Modelos , Transtornos da Percepção/genética , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/psicologia , Adolescente , Síndrome de Angelman/diagnóstico , Síndrome de Angelman/genética , Síndrome de Angelman/psicologia , Transtorno Autístico/diagnóstico , Transtorno Autístico/psicologia , Mapeamento Cromossômico , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/psicologia , Diagnóstico Diferencial , Feminino , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Deficiência Intelectual/psicologia , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Transtornos do Desenvolvimento da Linguagem/genética , Transtornos do Desenvolvimento da Linguagem/psicologia , Transtornos das Habilidades Motoras/diagnóstico , Transtornos das Habilidades Motoras/genética , Transtornos das Habilidades Motoras/psicologia , Testes Neuropsicológicos , Transtornos da Percepção/diagnóstico , Transtornos da Percepção/psicologia , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/psicologiaRESUMO
Ischemic and solid tumor tissues are less well perfused than normal tissue, leading to metabolic changes and chronic hypoxia, which in turn promotes angiogenesis. We identified human angiopoietin-like 4 (angptl4) as a gene with hypoxia-induced expression in endothelial cells. We showed that the levels of both mRNA and protein for ANGPTL4 increased in response to hypoxia. When tested in the chicken chorioallantoic membrane assay, ANGPTL4 induced a strong proangiogenic response, independently of vascular endothelial growth factor. In human pathology, ANGPTL4 mRNA is produced in ischemic tissues, in conditions such as critical leg ischemia. In tumors, ANGPTL4 is produced in the hypoxic areas surrounding necrotic regions. We observed particularly high levels of ANGPTL4 mRNA in tumor cells of conventional renal cell carcinoma. Other benign and malignant renal tumor cells do not produce ANGPTL4 mRNA. This molecule therefore seems to be a marker of conventional renal cell carcinoma. ANGPTL4, originally identified as a peroxisome proliferator-activated receptor alpha and gamma target gene, has potential for use as a new diagnostic tool and a potential therapeutic target, modulating angiogenesis both in tumors and in ischemic tissues. This study also suggests that ANGPTL4 may provide a link between metabolic disorders and hypoxia-induced angiogenesis.