RESUMO
De novo variants of ASH1L, which encodes a histone methyltransferase, have been reported in a few patients with intellectual disability and autistic features. Here, we identified a novel de novo frame-shift variant, c.2422_2423delAAinsT which predicts p.(Lys808TyrfsTer40), in ASH1L in a patient with multiple congenital anomalies (MCA), fine motor developmental delay, learning difficulties, attention deficit hyperactivity disorder, sleep apnea, and scoliosis. This frame-shift variant is expected to result in loss-of-function. Our report provides further evidence to support loss-of-function alterations of ASH1L as causative for an emergent neurodevelopmental syndrome characterized by MCA, intellectual disability, and behavioral problems, and further delineates this genetic disorder.
Assuntos
Anormalidades Múltiplas/genética , Proteínas de Ligação a DNA/genética , Deficiências do Desenvolvimento/genética , Mutação com Perda de Função , Fenótipo , Fatores de Transcrição/genética , Anormalidades Múltiplas/patologia , Criança , Deficiências do Desenvolvimento/patologia , Histona-Lisina N-Metiltransferase , Humanos , Masculino , SíndromeRESUMO
Despite current guidelines, few children with autism spectrum disorder (ASD) receive genetic evaluations. We surveyed Utah pediatricians to characterize the knowledge, beliefs, current practices and perceived barriers of pediatricians regarding genetic evaluation of children with ASD. We found over half lacked knowledge of current guidelines and many held beliefs about genetic evaluation that did not align with guidelines. Barriers were lack of insurance coverage for genetic evaluation/testing and long wait times to see geneticists. Pediatricians with beliefs aligned with guidelines and those aware of the role of genetic counselors were more likely to adhere to guidelines. Efforts to educate pediatricians are needed along with system level solutions regarding availability of geneticists and reimbursement for genetic testing.
