Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome.

Neurodevelopmental disorders, including autism spectrum disorder, have complex polygenic etiologies. Single-gene mutations in patients can help define genetic factors and molecular mechanisms underlying neurodevelopmental disorders. Here we describe individuals with monogenic heterozygous microdeletions in ANKS1B, a predicted risk gene for autism and neuropsychiatric diseases. Affected individuals present with a spectrum of neurodevelopmental phenotypes, including autism, attention-deficit hyperactivity disorder, and speech and motor deficits. Neurons generated from patient-derived induced pluripotent stem cells demonstrate loss of the ANKS1B-encoded protein AIDA-1, a brain-specific protein highly enriched at neuronal synapses. A transgenic mouse model of Anks1b haploinsufficiency recapitulates a range of patient phenotypes, including social deficits, hyperactivity, and sensorimotor dysfunction. Identification of the AIDA-1 interactome using quantitative proteomics reveals protein networks involved in synaptic function and the etiology of neurodevelopmental disorders. Our findings formalize a link between the synaptic protein AIDA-1 and a rare, previously undefined genetic disease we term ANKS1B haploinsufficiency syndrome.

Late cardiac assessment in children diagnosed with post-streptococcal reactive arthritis: a long term study.

OBJECTIVES: Unlike rheumatic fever (RF), the association of post-streptococcal reactive arthritis (PSRA) and carditis is controversial. The American Heart Association recommends anti-streptococcal prophylaxis for PSRA for one year, repeating echocardiogram and discontinuation of prophylaxis if normal. In this study the possibility of late cardiac involvement was investigated in a cohort of children with PSRA. METHODS: Children diagnosed with PSRA and followed at the Paediatric Rheumatology Units at two medical centres in Israel had echocardiography carried out by a paediatric cardiologist, at least 1 year following diagnosis. RESULTS: 146 patients with PSRA met the study criteria. Of these, 69 had undergone echocardiography 1-6.9 years (mean 3.6 years ± 1.5 years) after diagnosis. All had normal major parameters. Twenty (29.0%) patients had minimal cardiac findings, including 5 (7.2%) mild mitral insufficiency, 12 (17.4%) minimal mitral insufficiency, 2 (2.9%) mild tricuspid insufficiency and one patient (1.4%) had very mild, aortic insufficiency. Of the 77 patients who did not have echocardiography, 31 were randomly excluded from the initial study list, 26 refused to undergo echocardiography, and 20 were lost to follow-up. All were asymptomatic according to their medical record or telephone questionnaire. There were no significant differences in clinical or demographic data between those with or without echocardiography. CONCLUSIONS: No late cardiac involvement was found in our paediatric PSRA patients. Therefore, different approaches to antibiotic prophylaxis for PSRA and ARF are probably suggested. A prospective, controlled study is needed to definitively assess the necessity of prophylaxis in PSRA.

Effect of the characteristics of family physicians on their utilisation of laboratory tests.

BACKGROUND: The use of laboratory tests by family physicians has increased in recent years. AIMS: To evaluate the relationship between family physicians' characteristics and the number and type of laboratory tests requested, taking into account chronic diseases. DESIGN OF STUDY: Retrospective, cross-sectional study. SETTING: One hundred and sixty-two physicians treating 230 123 patients in one district of a health management organisation in Israel. METHOD: Physicians' use of 16 common types of laboratory tests was assessed in relation to physicians' demographic, professional, and clinic characteristics. The utilisation rate over 1 year was divided into quintiles for each laboratory test, and each physician was given a global laboratory score (for each test the physician got a score from 1 (utilisation in the lower quintile) to 5 (higher quintile). The global score was the sum of scores of the individual tests. RESULTS: On logistic regression analysis, four background characteristics were associated with the global score for the utilisation of laboratory tests. The highest hazard ratios were for being a female doctor (3.2, 95% confidence interval [CI] = 1.5 to 6.5), working in an urban clinic (3.2, 95% CI = 1.1 to 9.8), and having a greater workload than doctors in rural clinics (1.4, 95% CI = 1.1 to 1.8). Being a graduate of a Western country or Israel had a negative association with the global score (0.4, 95% CI = 0.1 to 0.99). CONCLUSION: Female sex and working in a urban clinic were major factors in the use of laboratory tests in clinical practice. As more women enter the medical profession, an improved understanding of the sex differences in ordering medical tests is important.