Frequency of the 7q11.23 inversion polymorphism in transmitting parents of children with Williams syndrome and in the general population does not differ between North America and Europe

Inversion of the Williams syndrome (WS) region on chromosome 7q11.23 has previously been shown to occur at a higher frequency in the transmitting parents of children with WS than in the general population, suggesting that it predisposes to the WS deletion. Frohnauer et al. recently reported that the frequency of this inversion is not elevated in the parents of children with WS in Germany relative to the German general population. We have compared Frohnauer et al.'s data to those from three previously published studies (Hobart et al., Bayes et al., Osborne et al.), all of which reported a significantly higher rate of 7q11.23 inversion in transmitting parents than in the general population. Results indicated that Frohnauer et al.'s data are consistent with previously reported frequencies of 7q11.23 inversion in North America and Spain in both transmitting parents and the general population

Effects of Nonresponse on the Mean Squared Error of Estimates from a Longitudinal Study

Research in this study focuses on two related aspects of unit nonresponse (nonresponse by sampled members of study populations) in the rounds of the National Longitudinal Study of Adolescent Health (Add Health) (Chantala and Tabor, 1999): (i) round-specific nonresponse bias and its component contributions, and (ii) the statistical utility of alternative approaches to adjusting sample weights for nonresponse. This work is part of four research studies funded by CDC-NCHS, at the UNC Center for Health Statistics Research. Nonrespondents in surveys can be classified according to the reason for nonresponse (Lessler and Kalsbeek, 1992): 1) Not Solicited (NS): Sample members are not solicited as perhaps their address is unknown, or they are out of the country; 2) Solicited but Unable (SUA): Sample members are contacted but decline to participate based on inability. Reasons include physical or language limitations; 3) Solicited but Unwilling (SUW): Sample members are contacted but refuse to participate for reasons such as lack of time or, apathy; and 4) Other Nonrespondents (OTH): Sample nonrespondents give a reason that does not fit in any of the previous categories. Examples are lost schedules and partial respondents Response outcome information and data to obtain 13 different measures of health risk from Add Health are used to accomplish two main tasks in this study. First, we estimate the round-specific nonresponse bias and its component contributions corresponding to the four nonresponse categories described. The sign (negative or positive) of these components and the offsetting effects of some components on the overall bias is of particular interest. Second, we compare the statistical effects of alternate sample adjustments for nonresponse on the bias and variance of study estimates. It is important to note here that we are examining the effects of nonresponse in IH1 and IH2 separately, and not the cumulative effects of nonresponse through these rounds

Three-weekly doses of azithromycin for Indigenous infants hospitalized with bronchiolitis: a multicentre, randomized, placebo-controlled trial

Background: Bronchiolitis is a major health burden in infants globally, particularly among Indigenous populations. It is unknown if 3 weeks of azithromycin improve clinical outcomes beyond the hospitalization period. In an international, double-blind randomized controlled trial, we determined if 3 weeks of azithromycin improved clinical outcomes in Indigenous infants hospitalized with bronchiolitis.Methods: Infants aged ≤24 months were enrolled from three centers and randomized to receive three once-weekly doses of either azithromycin (30 mg/kg) or placebo. Nasopharyngeal swabs were collected at baseline and 48 h later. Primary endpoints were hospital length of stay (LOS) and duration of oxygen supplementation monitored every 12 h until judged ready for discharge. Secondary outcomes were: day-21 symptom/signs, respiratory rehospitalizations within 6 months post-discharge and impact upon nasopharyngeal bacteria and virus shedding at 48 h.Results: Two hundred nineteen infants were randomized (n = 106 azithromycin, n = 113 placebo). No significant between-group differences were found for LOS (median 54 h for each group, difference = 0 h, 95% CI: −6, 8; p = 0.8), time receiving oxygen (azithromycin = 40 h, placebo = 35 h, group difference = 5 h, 95% CI: −8, 11; p = 0.7), day-21 symptom/signs, or rehospitalization within 6 months (azithromycin n = 31, placebo n = 25 infants, p = 0.2). Azithromycin reduced nasopharyngeal bacterial carriage (between-group difference 0.4 bacteria/child, 95% CI: 0.2, 0.6; p < 0.001), but had no significant effect upon virus detection rates.Conclusion: Despite reducing nasopharyngeal bacterial carriage, three large once-weekly doses of azithromycin did not confer any benefit over placebo during the bronchiolitis illness or 6 months post hospitalization. Azithromycin should not be used routinely to treat infants hospitalized with bronchiolitis.Clinical trial registration: The trial was registered with the Australian and New Zealand Clinical Trials Register: Clinical trials number: ACTRN1261000036099

Genome Rearrangements Detected by SNP Microarrays in Individuals with Intellectual Disability Referred with Possible Williams Syndrome

Intellectual disability (ID) affects 2-3% of the population and may occur with or without multiple congenital anomalies (MCA) or other medical conditions. Established genetic syndromes and visible chromosome abnormalities account for a substantial percentage of ID diagnoses, although for approximately 50% the molecular etiology is unknown. Individuals with features suggestive of various syndromes but lacking their associated genetic anomalies pose a formidable clinical challenge. With the advent of microarray techniques, submicroscopic genome alterations not associated with known syndromes are emerging as a significant cause of ID and MCA.High-density SNP microarrays were used to determine genome wide copy number in 42 individuals: 7 with confirmed alterations in the WS region but atypical clinical phenotypes, 31 with ID and/or MCA, and 4 controls. One individual from the first group had the most telomeric gene in the WS critical region deleted along with 2 Mb of flanking sequence. A second person had the classic WS deletion and a rearrangement on chromosome 5p within the Cri du Chat syndrome (OMIM:123450) region. Six individuals from the ID/MCA group had large rearrangements (3 deletions, 3 duplications), one of whom had a large inversion associated with a deletion that was not detected by the SNP arrays.Combining SNP microarray analyses and qPCR allowed us to clone and sequence 21 deletion breakpoints in individuals with atypical deletions in the WS region and/or ID or MCA. Comparison of these breakpoints to databases of genomic variation revealed that 52% occurred in regions harboring structural variants in the general population. For two probands the genomic alterations were flanked by segmental duplications, which frequently mediate recurrent genome rearrangements; these may represent new genomic disorders. While SNP arrays and related technologies can identify potentially pathogenic deletions and duplications, obtaining sequence information from the breakpoints frequently provides additional information

Not All Side Effects Associated With Tricyclic Antidepressant Therapy Are True Side Effects

Patients with functional gastrointestinal (GI) disorders treated with tricyclic antidepressants may report non-GI symptoms. It is unclear whether these symptoms are side effects of the medication or reflect a general behavioral tendency to report symptoms. This study 1) evaluated whether a checklist of symptoms reported by patients prior to taking desipramine increased in number or worsened in severity after being on a tricyclic antidepressant (desipramine), and 2) assessed baseline factors that predispose patients to report symptoms

A Very Low-Carbohydrate Diet Improves Symptoms and Quality of Life in Diarrhea-Predominant Irritable Bowel Syndrome

Patients with diarrhea-predominant IBS (IBS-D) anecdotally report symptom improvement after initiating a very low-carbohydrate diet (VLCD). This is the first study to prospectively evaluate a VLCD in IBS-D

Rare and Low Frequency Genomic Variants Impacting Neuronal Functions Modify the Dup7q11.23 Phenotype

© 2021, The Author(s). Background: 7q11.23 duplication (Dup7) is one of the most frequent recurrent copy number variants (CNVs) in individuals with autism spectrum disorder (ASD), but based on gold-standard assessments, only 19% of Dup7 carriers have ASD, suggesting that additional genetic factors are necessary to manifest the ASD phenotype. To assess the contribution of additional genetic variants to the Dup7 phenotype, we conducted whole-genome sequencing analysis of 20 Dup7 carriers: nine with ASD (Dup7-ASD) and 11 without ASD (Dup7-non-ASD). Results: We identified three rare variants of potential clinical relevance for ASD: a 1q21.1 microdeletion (Dup7-non-ASD) and two deletions which disrupted IMMP2L (one Dup7-ASD, one Dup7-non-ASD). There were no significant differences in gene-set or pathway variant burden between the Dup7-ASD and Dup7-non-ASD groups. However, overall intellectual ability negatively correlated with the number of rare loss-of-function variants present in nervous system development and membrane component pathways, and adaptive behaviour standard scores negatively correlated with the number of low-frequency likely-damaging missense variants found in genes expressed in the prenatal human brain. ASD severity positively correlated with the number of low frequency loss-of-function variants impacting genes expressed at low levels in the brain, and genes with a low level of intolerance. Conclusions: Our study suggests that in the presence of the same pathogenic Dup7 variant, rare and low frequency genetic variants act additively to contribute to components of the overall Dup7 phenotype

LIM-kinase1 Hemizygosity Implicated in Impaired Visuospatial Constructive Cognition

AbstractTo identify genes important for human cognitive development, we studied Williams syndrome (WS), a developmental disorder that includes poor visuospatial constructive cognition. Here we describe two families with a partial WS phenotype; affected members have the specific WS cognitive profile and vascular disease, but lack other WS features. Submicroscopic chromosome 7q11.23 deletions cosegregate with this phenotype in both families. DNA sequence analyses of the region affected by the smallest deletion (83.6 kb) revealed two genes, elastin (ELN ) and LIM-kinase1 (LIMK1). The latter encodes a novel protein kinase with LIM domains and is strongly expressed in the brain. Because ELN mutations cause vascular disease but not cognitive abnormalities, these data implicate LIMK1 hemizygosity in impaired visuospatial constructive cognition

International Survey of Patients With IBS: Symptom Features and Their Severity, Health Status, Treatments, and Risk Taking to Achieve Clinical Benefit

While clinicians generally make treatment decisions in IBS related to the type of symptoms, other factors such as the perceived severity and the risks patients are willing to tolerate for effective treatment are also important to consider. These factors are not fully understood

The tyranny of the male preserve

Within this paper I draw on short vignettes and quotes taken from a two-year ethnographic study of boxing to think through the continuing academic merit of the notion of the male preserve. This is an important task due to evidence of shifts in social patterns of gender that have developed since the idea was first proposed in the 1970s. In aligning theoretical contributions from Lefebvre and Butler to discussions of the male preserve, we are able to add nuance to our understanding of how such social spaces are engrained with and produced by the lingering grasp of patriarchal narratives. In particular, by situating the male preserve within shifting social processes, whereby certain men’s power is increasingly undermined, I highlight the production of space within which narratives connecting men to violence, aggression and physical power can be consumed, performed and reified in a relatively unrestricted form. This specific case study contributes to gender theory as an illustration of a way in which we might explore and understand social enclaves where certain people are able to lay claim to space and power. As such, I argue that the notion of the male preserve is still a useful conceptual, theoretical and political device especially when considered as produced by the tyranny of gender power through the dramatic representation and reification of behaviours symbolically linked to patriarchal narrations of manhood