Daptomycin exerts bactericidal effect through induction of excessive ROS production and blocking the function of stress response protein Usp2

202207 bckwVersion of RecordRGCPublishe

Practical guidelines for managing adults with 22q11.2 deletion synddrome

22q11.2 Deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans, estimated to affect up to 1 in 2,000 live births. Major features of this multisystem condition include congenital anomalies, developmental delay, and an array of early- and later-onset medical and psychiatric disorders. Advances in pediatric care ensure a growing population of adults with 22q11.2DS. Informed by an international panel of multidisciplinary experts and a comprehensive review of the existing literature concerning adults, we present the first set of guidelines focused on managing the neuropsychiatric, endocrine, cardiovascular, reproductive, psychosocial, genetic counseling, and other issues that are the focus of attention in adults with 22q11.2DS. We propose practical strategies for the recognition, evaluation, surveillance, and management of the associated morbidities.Genet Med 17 8, 599-60

Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome

The 22q11.2 deletion syndrome (22q11DS) is associated with a 20-25% risk of schizophrenia. In a cohort of 962 individuals with 22q11DS, we examined the shared genetic basis between schizophrenia and schizophrenia-related early trajectory phenotypes: sub-threshold symptoms of psychosis, low baseline intellectual functioning and cognitive decline. We studied the association of these phenotypes with two polygenic scores, derived for schizophrenia and intelligence, and evaluated their use for individual risk prediction in 22q11DS. Polygenic scores were not only associated with schizophrenia and baseline intelligence quotient (IQ), respectively, but schizophrenia polygenic score was also significantly associated with cognitive (verbal IQ) decline and nominally associated with sub-threshold psychosis. Furthermore, in comparing the tail-end deciles of the schizophrenia and IQ polygenic score distributions, 33% versus 9% of individuals with 22q11DS had schizophrenia, and 63% versus 24% of individuals had intellectual disability. Collectively, these data show a shared genetic basis for schizophrenia and schizophrenia-related phenotypes and also highlight the future potential of polygenic scores for risk stratification among individuals with highly, but incompletely, penetrant genetic variants

22q11.2 Deletions in Patients with Conotruncal Defects: Data from 1,610 Consecutive Cases

BACKGROUND: The 22q11.2 deletion syndrome is characterized by multiple congenital anomalies including conotruncal cardiac defects. Identifying the patient with a 22q11.2 deletion (22q11del) can be challenging because many extracardiac features become apparent later in life. We sought to better define the cardiac phenotype associated with a 22q11del to help direct genetic testing. METHODS: 1,610 patients with conotruncal defects were sequentially tested for a 22q11del. Counts and frequencies for primary lesions and cardiac features were tabulated for those with and without a 22q11del. Logistic regression models investigated cardiac features that predicted deletion status in tetralogy of Fallot (TOF). RESULTS: Deletion frequency varied by primary anatomic phenotype. Regardless of the cardiac diagnosis, a concurrent aortic arch anomaly (AAA) was strongly associated with deletion status (OR 5.07, 95% CI: 3.66–7.04). In the TOF subset, the strongest predictor of deletion status was an AAA (OR 3.14, 95% CI: 1.87–5.27, p <0.001), followed by pulmonary valve atresia (OR 2.03, 95% CI: 1.02–4.02, p= 0.04). Among those with double outlet right ventricle and transposition of the great arteries, only those with an AAA had a 22q11del. However, five percent of patients with an isolated conoventricular ventricular septal defect and normal aortic arch anatomy had a 22q11del, while no one with an IAA-A had a 22q11del. CONCLUSION: A subset of patients with conotruncal defects are at risk for a 22q11del. A concurrent AAA increases the risk regardless of the intracardiac anatomy. These findings help direct genetic screening for the 22q11.2 deletion syndrome in the cardiac patient