PurposeThe purpose of the current study was to assess the penetrance of NRXN1 deletions.MethodsWe compared the prevalence and genomic extent of NRXN1 deletions identified among 19,263 clinically referred cases to that of 15,264 controls. The burden of additional clinically relevant CNVs was used as a proxy to estimate the relative penetrance of NRXN1 deletions.ResultsWe identified 41 (0.21%) previously unreported exonic NRXN1 deletions ascertained for developmental delay/intellectual disability, significantly greater than in controls [OR=8.14 (95% CI 2.91–22.72), p< 0.0001)]. Ten (22.7%) of these had a second clinically relevant CNV. Subjects with a deletion near the 3′ end of NRXN1 were significantly more likely to have a second rare CNV than subjects with a 5′ NRXN1 deletion [OR=7.47 (95% CI 2.36–23.61), p=0.0006]. The prevalence of intronic NRXN1 deletions was not statistically different between cases and controls (p=0.618). The majority (63.2%) of intronic NRXN1 deletion cases had a second rare CNV, a two-fold greater prevalence than for exonic NRXN1 deletion cases (p=0.0035).ConclusionsThe results support the importance of exons near the 5′ end of NRXN1 in the expression of neurodevelopmental disorders. Intronic NRXN1 deletions do not appear to substantially increase the risk for clinical phenotypes.

PEs add a powerful real-life dimension to communication skills teaching and have been shown to be a valuable educational modality. Moreover, exposure to and reflection on video-based patient narratives are useful ways of teaching medical students about patients' lived experiences and promoting person-centered communication, both within and beyond IDD.

BackgroundSchizophrenia is a severe psychiatric disorder associated with IQ deficits. Rare copy number variations (CNVs) have been established to play an important role in the etiology of schizophrenia. Several of the large rare CNVs associated with schizophrenia have been shown to negatively affect IQ in population-based controls where no major neuropsychiatric disorder is reported. The aim of this study was to examine the diagnostic yield of microarray testing and the functional impact of genome-wide rare CNVs in a community ascertained cohort of adults with schizophrenia and low (< 85) or average (≥ 85) IQ.MethodsWe recruited 546 adults of European ancestry with schizophrenia from six community psychiatric clinics in Canada. Each individual was assigned to the low or average IQ group based on standardized tests and/or educational attainment. We used rigorous methods to detect genome-wide rare CNVs from high-resolution microarray data. We compared the burden of rare CNVs classified as pathogenic or as a variant of unknown significance (VUS) between each of the IQ groups and the genome-wide burden and functional impact of rare CNVs after excluding individuals with a pathogenic CNV.ResultsThere were 39/546 (7.1%; 95% confidence interval [CI] = 5.2–9.7%) schizophrenia participants with at least one pathogenic CNV detected, significantly more of whom were from the low IQ group (odds ratio [OR] = 5.01 [2.28–11.03], p = 0.0001). Secondary analyses revealed that individuals with schizophrenia and average IQ had the lowest yield of pathogenic CNVs (n = 9/325; 2.8%), followed by those with borderline intellectual functioning (n = 9/130; 6.9%), non-verbal learning disability (n = 6/29; 20.7%), and co-morbid intellectual disability (n = 15/62; 24.2%). There was no significant difference in the burden of rare CNVs classified as a VUS between any of the IQ subgroups. There was a significantly (p=0.002) increased burden of rare genic duplications in individuals with schizophrenia and low IQ that persisted after excluding individuals with a pathogenic CNV.ConclusionsUsing high-resolution microarrays we were able to demonstrate for the first time that the burden of pathogenic CNVs in schizophrenia differs significantly between IQ subgroups. The results of this study have implications for clinical practice and may help inform future rare variant studies of schizophrenia using next-generation sequencing technologies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-017-0488-z) contains supplementary material, which is available to authorized users.

The information in this column is not intended as a definitive treatment

HIV infection and AIDS: the ethics of medical confidentiality Kenneth M Boyd Secretary, IME working party, on behalf of the working party Author's abstract An Institute ofMedical Ethics working party argues that an ethically desirable relationship ofmutual empowerment between patient and clinician is more likely to be achieved ifpatients understand the ground rules ofmedical confidentiality. It identifies and illustrates ambiguities in the General Medical Council's guidance on AIDS and confidentiality, and relates this to the practice ofdifferent doctors and specialties. Matters might be clarified, it suggests, by identifying moralfactors which tend to recur in medical decisions about maintaining or breaching confidentiality. The working party argues that two such factors are particularly important: the patient's need to exercise informed choice and the doctor's primary responsibility to his or her own patients. Medical confidentiality and discretion 'All that may come to my knowledge in the exercise of my profession or outside of my profession or in daily commerce with men, which ought not to be spread abroad, I will keep secret and will never reveal' (1). The modern Declaration of Geneva reformulates this clause from the Hippocratic Oath as, 'I will respect the secrets which are confided in me, even after the patient has died' (2). These statements show that the medical profession continues to regard confidentiality as a very important moral duty, but does not consider it an absolute one. The Hippocratic Oath is concerned with discretion as well as with confidentiality, and limits both to what 'ought not to be spread abroad'. The Geneva version, restricted to 'secrets which are confided in me', promises to 'respect' rather than to 'never reveal' them. Both statements, that is, imply that the duty of confidentiality may be qualified by other considerations. Neither version specifies what these considerations might be: but current disciplinary guidelines allow doctors to disclose confidential information in certain exceptional circumstances, when this is judged to be in the interest of the patient