Genetic analyses of patients with transposition of the great arteries have identified rare copy number variations,suggesting that they may be significant to the aetiology of the disease.This paper reports the identifi...Genetic analyses of patients with transposition of the great arteries have identified rare copy number variations,suggesting that they may be significant to the aetiology of the disease.This paper reports the identification of a 16 p11.2 microduplication,a variation that has yet to be reported in association with transposition of the great arteries.The 16 p11.2 microduplication is associated with autism spectrum disorder and developmental delay,but with highly variable phenotypic effects.Autism and attention deficit disorders are observed more frequently in children with congenital heart disease than in the general population.Neonatal surgery is proposed as a risk factor,but as yet unidentified genetic abnormalities should also be taken into account.Thus,congenital heart abnormalities may constitute a part of the phenotypic spectrum associated with duplications at 16 p11.2.We suggest chromosomal microarray be considered part of the diagnostic work-up in patients with transposition of the great arteries.展开更多
Since Autism Spectrum Disorder (ASD) is strongly associated with chromosomal abnormalities of 16p11.2, and Autism has been linked to neuronal polarity defect, our study aimed to explore the role of 16p11.2 genes in re...Since Autism Spectrum Disorder (ASD) is strongly associated with chromosomal abnormalities of 16p11.2, and Autism has been linked to neuronal polarity defect, our study aimed to explore the role of 16p11.2 genes in regulating neuronal polarity. We performed a neuronal polarity assay in a high throughput manner for candidate genes at 16p11.2. Our most interesting finding was that three 16p11.2 candidate genes, DOC2a, Tbx-6 and KIF 22, affected neuronal polarity. Our research, for the first time, indicates a novel association between 16p11.2 and neuronal polarity. Our results support the hypothesis that 16p11.2 is required for neuronal polarity. Our research provides new important insights into molecular mechanisms underlying the tight association between 16p11.2 and several neural developmental disorders, including autism, epilepsy, mental retardation and schizophrenia.展开更多
Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on ou...Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on our ability to identify and screen high-risk populations before their symptoms arise. Risk factors for developing pancreatic cancer include multiple genetic syndromes as well as modifiable risk factors. Genetic conditions include hereditary breast and ovarian cancer syndrome, Lynch Syndrome, familial adenomatous polyposis, Peutz-Jeghers Syndrome, familial atypical multiple mole melanoma syndrome, hereditary pancreatitis, cystic fibrosis, and ataxia-telangiectasia; having a genetic predisposition can raise the risk of developing pancreatic cancer up to 132-fold over the general population. Modifiable risk factors, which include tobacco exposure, alcohol use, chronic pancreatitis, diet, obesity, diabetes mellitus, as well as certain abdominal surgeries and infections, have also been shown to increase the risk of pancreatic cancer development. Several largevolume centers have initiated such screening protocols, and consensus-based guidelines for screening high-riskgroups have recently been published. The focus of this review will be both the genetic and modifiable risk factors implicated in pancreatic cancer, as well as a review of screening strategies and their diagnostic yields.展开更多
文摘Genetic analyses of patients with transposition of the great arteries have identified rare copy number variations,suggesting that they may be significant to the aetiology of the disease.This paper reports the identification of a 16 p11.2 microduplication,a variation that has yet to be reported in association with transposition of the great arteries.The 16 p11.2 microduplication is associated with autism spectrum disorder and developmental delay,but with highly variable phenotypic effects.Autism and attention deficit disorders are observed more frequently in children with congenital heart disease than in the general population.Neonatal surgery is proposed as a risk factor,but as yet unidentified genetic abnormalities should also be taken into account.Thus,congenital heart abnormalities may constitute a part of the phenotypic spectrum associated with duplications at 16 p11.2.We suggest chromosomal microarray be considered part of the diagnostic work-up in patients with transposition of the great arteries.
文摘Since Autism Spectrum Disorder (ASD) is strongly associated with chromosomal abnormalities of 16p11.2, and Autism has been linked to neuronal polarity defect, our study aimed to explore the role of 16p11.2 genes in regulating neuronal polarity. We performed a neuronal polarity assay in a high throughput manner for candidate genes at 16p11.2. Our most interesting finding was that three 16p11.2 candidate genes, DOC2a, Tbx-6 and KIF 22, affected neuronal polarity. Our research, for the first time, indicates a novel association between 16p11.2 and neuronal polarity. Our results support the hypothesis that 16p11.2 is required for neuronal polarity. Our research provides new important insights into molecular mechanisms underlying the tight association between 16p11.2 and several neural developmental disorders, including autism, epilepsy, mental retardation and schizophrenia.
文摘Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on our ability to identify and screen high-risk populations before their symptoms arise. Risk factors for developing pancreatic cancer include multiple genetic syndromes as well as modifiable risk factors. Genetic conditions include hereditary breast and ovarian cancer syndrome, Lynch Syndrome, familial adenomatous polyposis, Peutz-Jeghers Syndrome, familial atypical multiple mole melanoma syndrome, hereditary pancreatitis, cystic fibrosis, and ataxia-telangiectasia; having a genetic predisposition can raise the risk of developing pancreatic cancer up to 132-fold over the general population. Modifiable risk factors, which include tobacco exposure, alcohol use, chronic pancreatitis, diet, obesity, diabetes mellitus, as well as certain abdominal surgeries and infections, have also been shown to increase the risk of pancreatic cancer development. Several largevolume centers have initiated such screening protocols, and consensus-based guidelines for screening high-riskgroups have recently been published. The focus of this review will be both the genetic and modifiable risk factors implicated in pancreatic cancer, as well as a review of screening strategies and their diagnostic yields.
