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The French-Canadian population of Saguenay-Lac-Saint-Jean is known for its homogenous genetic background. The hereditary causes of hearing loss were previously unexplored in this population. Individuals with hearing loss were referred from the otorhinolaryngology, pediatrics and family physicians' clinics to the medical genetics service at the Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-Saint-Jean between June 2015 and March 2021. A regional clinical evaluation strategy was developed. Samples from 63 individuals belonging to 41 families were sent independently to different molecular clinical laboratories and index cases were analyzed through comprehensive multigene panels, with a diagnostic rate of 54%. Sixteen hearing loss causal variants were identified in 12 genes, with eight of these variants not been previously reported in the literature. Recurrent variants were present in four genes, suggesting a possible founder effect, while GJB2 gene variants were scarce. A comprehensive multigene panel approach as part of the proposed clinical evaluation strategy offers a high diagnostic yield for this population.

Drug overdoses were a leading cause of injury and death in the United States in 2021. Solitary drug use and solitary overdose deaths have remained persistent challenges warranting additional attention throughout the overdose epidemic. The goal of this narrative review is to describe recent global innovations in overdose detection technologies (ODT) enabling rapid responses to overdose events, especially for people who use drugs alone. We found that only a small number of technologies designed to assist in overdose detection and response are currently commercially available, though several are in the early stages of development. Research, development, and scale-up of practical, cost-effective ODTs remains a public health imperative. Equipping places where people live, learn, work, worship, and play with the necessary tools to detect and prevent overdose deaths could complement ongoing overdose prevention efforts.

Face-recognition abilities differ largely in the neurologically typical population. We examined how the use of information varies with face-recognition ability from developmental prosopagnosics to super-recognizers. Specifically, we investigated the use of facial features at different spatial scales in 112 individuals, including 5 developmental prosopagnosics and 8 super-recognizers, during an online famous-face-identification task using the bubbles method. We discovered that viewing of the eyes and mouth to identify faces at relatively high spatial frequencies is strongly correlated with face-recognition ability, evaluated from two independent measures. We also showed that the abilities of developmental prosopagnosics and super-recognizers are explained by a model that predicts face-recognition ability from the use of information built solely from participants with intermediate face-recognition abilities ( n = 99). This supports the hypothesis that the use of information varies quantitatively from developmental prosopagnosics to super-recognizers as a function of face-recognition ability.

The Campbell-Robson chart is a highly popular figure used in psychophysics and visual perception textbooks to illustrate the Contrast Sensitivity Function (CSF). The chart depicts a grating which varies logarithmically in spatial frequency (SF) from left to right and in contrast from bottom to top. Campbell and Robson’s (1964) intuition was that the boundary between the grating and the homogeneous gray area (below threshold) would trace the shape of the observer’s own CSF. In this paper, we tested this intuition. A total of 170 participants (96 adults and 74 children) adjusted the four parameters of a truncated log-parabola directly onto a Campbell-Robson chart rendition and completed a gold-standard CSF evaluation. We hoped that this procedure which requires a mere three clicks on the computer mouse, would speed up the measurement of the CSF to under a minute. Unfortunately, the only parameter of the truncated log-parabola fitted to the gold-standard CSF data that could be predicted from the Campbell-Robson chart data was the peak sensitivity for the adult participants. We conclude that the curve visible on the Campbell-Robson chart cannot be used practically to measure the CSF.

Purpose: Biallelic variants in TBC1D24, which encodes a protein that regulates vesicular transport, are frequently identified in patients with DOORS (deafness, onychodystrophy, osteodystrophy, intellectual disability [previously referred to as mental retardation], and seizures) syndrome. The aim of the study was to identify a genetic cause in families with DOORS syndrome and without a TBC1D24 variant. Methods: Exome or Sanger sequencing was performed in individuals with a clinical diagnosis of DOORS syndrome without TBC1D24 variants. Results: We identified the same truncating variant in ATP6V1B2 (NM_001693.4:c.1516C>T; p.Arg506*) in nine individuals from eight unrelated families with DOORS syndrome. This variant was already reported in individuals with dominant deafness onychodystrophy (DDOD) syndrome. Deafness was present in all individuals, along with onychodystrophy and abnormal fingers and/or toes. All families but one had developmental delay or intellectual disability and five individuals had epilepsy. We also describe two additional families with DDOD syndrome in whom the same variant was found. Conclusion: We expand the phenotype associated with ATP6V1B2 and propose another causal gene for DOORS syndrome. This finding suggests that DDOD and DOORS syndromes might lie on a spectrum of clinically and molecularly related conditions.

Approximately one in every 200 mammalian proteins is anchored to the cell membrane through a glycosylphosphatidylinositol (GPI) anchor. These proteins play important roles notably in neurological development and function. To date, more than 20 genes have been implicated in the biogenesis of GPI-anchored proteins. GPAA1 (glycosylphosphatidylinositol anchor attachment 1) is an essential component of the transamidase complex along with PIGK, PIGS, PIGT, and PIGU (phosphatidylinositol-glycan biosynthesis classes K, S, T, and U, respectively). This complex orchestrates the attachment of the GPI anchor to the C terminus of precursor proteins in the endoplasmic reticulum. Here, we report bi-allelic mutations in GPAA1 in ten individuals from five families. Using whole-exome sequencing, we identified two frameshift mutations (c.981_993del [p.Gln327Hisfs∗102] and c.920delG [p.Gly307Alafs∗11]), one intronic splicing mutation (c.1164+5C>T), and six missense mutations (c.152C>T [p.Ser51Leu], c.160_161delinsAA [p.Ala54Asn], c.527G>C [p.Trp176Ser], c.869T>C [p.Leu290Pro], c.872T>C [p.Leu291Pro], and c.1165G>C [p.Ala389Pro]). Most individuals presented with global developmental delay, hypotonia, early-onset seizures, cerebellar atrophy, and osteopenia. The splicing mutation was found to decrease GPAA1 mRNA. Moreover, flow-cytometry analysis of five available individual samples showed that several GPI-anchored proteins had decreased cell-surface abundance in leukocytes (FLAER, CD16, and CD59) or fibroblasts (CD73 and CD109). Transduction of fibroblasts with a lentivirus encoding the wild-type protein partially rescued the deficiency of GPI-anchored proteins. These findings highlight the role of the transamidase complex in the development and function of the cerebellum and the skeletal system.

Study design Retrospective study of a series of 286 patients with congenital scoliosis (CS). Objective To describe a large cohort of patients with CS and to propose an algorithm for genetic investigations SUMMARY OF BACKGROUND DATA.: CS is characterized by a spine curvature due to congenital malformations of the vertebrae and is frequently associated to other anomalies. The underlying causes remain unclear in most patients, although we know that genetics plays a role in the development of vertebral defects. Methods Institutional review board approval was obtained. We performed a retrospective study by consulting the hospital charts of 286 patients with CS seen at the CHU Sainte-Justine, Montreal, from 2004 to 2015. We compile information on radiological findings, associated malformations, and genetic tests. Results Results showed that 67.1% of patients had associated anomalies affecting different systems. Only a minority of patients had a syndromic diagnosis to explain their CS. Nevertheless, array comparative genomic hybridization performed in a minority of patients showed a high detection rate (31.3% had a chromosomal anomaly among 32 tested). Conclusion We suggest that every patient with CS should have thorough investigations to rule out associated anomalies and that different genetic tests should be offered according to the associated clinical findings. Level of evidence 4.

A pilot population-based carrier screening program started in 2010 in the Saguenay-Lac-Saint-Jean region of Quebec, Canada, for four recessive diseases with local founder effects (tyrosinemia type I, autosomal recessive spastic ataxia of Charlevoix-Saguenay, congenital lactic acidosis, and Andermann syndrome). Objectives The objective of this study was to describe the experience of carrier couples identified through this program. Methods Semi-structured interviews were performed with carrier couples. Thematic analysis of interview transcripts was performed to identify emerging themes. Results Interviews were performed with 15 carrier couples (56% response rate). Carrier couples had little knowledge about the target diseases before being identified as carriers, despite pre-test education sessions. The main motivation for screening was a recommendation by a peer who had been screened, even for those with a positive family history of one of the target conditions. Couples perceived themselves at low risk of being a carrier couple, whatever their family history. Being found to be a carrier couple was initially a shock, illustrating how ill prepared they were for such a result, but carrier couples appreciated knowing their status. Conclusion Our results emphasize the informational needs of couples to make informed decisions and the importance of post-test counseling for those with positive results. Our findings can inform counseling procedures in expanded carrier screening. © 2017 John Wiley & Sons, Ltd.

Many studies have revealed cultural differences in the way Easterners and Westerners attend to their visual world. It has been proposed that these cultural differences reflect the utilization of different processes, namely holistic processes by Easterners and analytical processes by Westerners. In the face processing literature, eye movement studies have revealed different fixation patterns for Easterners and Westerners that are congruent with a broader spread of attention by Easterners: compared with Westerners, Easterners tend to fixate more toward the center of the face even if they need the information provided by the eyes and mouth. Although this cultural difference could reflect an impact of culture on the visual mechanisms underlying face processing, this interpretation has been questioned by the finding that Easterners and Westerners do not differ on the location of their initial fixations, that is, those that have been shown as being sufficient for face recognition. Because a broader spread of attention is typically linked with the reduced sensitivity to higher spatial frequency, the present study directly compared the spatial frequency tuning of Easterners (Chinese) and Westerners (Canadians) in 2 face recognition tasks (Experiment 1 and 2), along with their general low-level sensitivity to spatial frequencies (Experiment 3). Consistent with our hypothesis, Chinese participants were tuned toward lower spatial frequencies than Canadians participants during the face recognition tasks, despite comparable low-level contrast sensitivity functions. These results strongly support the hypothesis that culture impacts the nature of the visual information extracted during face recognition. (PsycINFO Database Record

Objective: A large number of children report fear and distress when undergoing blood work and intravenous placement. In pediatric departments, Child Life interventions are considered to be the gold standard in nonmedical pain management techniques. Virtual reality (VR) has also been identified as an effective tool for pain distraction in children undergoing painful medical procedures. The aim of this study was to document the efficacy of VR as a mode of distraction during a medical procedure compared with two comparison conditions: watching television (TV, minimal control condition) and distraction provided by the Child Life (CL, gold standard control condition) program. Materials and Methods: A total of 59 children aged 8-17 years (35% female) were recruited through the emergency department (ED) of the Children's Hospital of Eastern Ontario and randomly assigned to one of the three conditions. The key outcome measures were visual analog scale ratings of pain intensity and fear of pain, administrated before and right after the procedure. Patient satisfaction was also measured after the intervention. Results: A significant reduction in fear of pain and pain intensity was reported in all three conditions. A larger and statistically significant reduction in fear of pain was observed among children who used VR distraction compared with the CL and TV conditions, but this effect was not observed for pain intensity. The children's satisfaction with the VR procedure was significantly higher than for TV and comparable to CL. Discussion: The advantages of using VR in the ED to manage pain in children are discussed.

Leigh syndrome French Canadian type (LSFC) is a mitochondrial disease caused by mutations in the leucine-rich pentatricopeptide repeat-containing (LRPPRC) gene leading to a reduction of cytochrome-c oxidase (COX) expression reaching 50% in skin fibroblasts. We have shown that under basal conditions, LSFC and control cells display similar ATP levels. We hypothesized that this occurs through upregulation of mechanistic target of rapamycin (mTOR)-mediated metabolic reprogramming. Our results showed that compared with controls, LSFC cells exhibited an upregulation of the mTOR complex 1 (mTORC1)/p70 ribosomal S6 kinase pathway and higher levels of hypoxia-inducible factor 1α (HIF-1α) and its downstream target pyruvate dehydrogenase kinase 1 (PDHK1), a regulator of mitochondrial pyruvate dehydrogenase 1 (PDH1). Consistent with these signaling alterations, LSFC cells displayed a 40–61% increase in [U-(13)C(6)]glucose contribution to pyruvate, lactate, and alanine formation, as well as higher levels of the phosphorylated and inactive form of PDH1-α. Interestingly, inhibition of mTOR with rapamycin did not alter HIF-1α or PDHK1 protein levels in LSFC fibroblasts. However, this treatment increased PDH1-α phosphorylation in control and LSFC cells and reduced ATP levels in control cells. Rapamycin also decreased LRPPRC expression by 41 and 11% in LSFC and control cells, respectively, and selectively reduced COX subunit IV expression in LSFC fibroblasts. Taken together, our data demonstrate the importance of mTORC1, independent of the HIF-1α/PDHK1 axis, in maintaining LRPPRC and COX expression in LSFC cells.

The objective of the present study is to describe a cohort of complex esophageal atresia and the yield of genetic tests performed for such patients. We selected 45 patients with complex esophageal atresia (EA), namely those having at least one associated anomaly. We reviewed their medical records to assess clinical features, other diagnoses, and genetic investigations. Most of the patients had a diagnosis of VACTERL association (56%) with no genetic variant identified. Interestingly, 5 patients in the cohort (11%) had a right pulmonary hypoplasia or agenesis. A majority of our cohort (73%) had genetic testing; 60% were karyotyped (abnormal in 4 of the 27 patients tested), 31% had aCGH (abnormal in 1 of the 14 patients tested), and 31% had diepoxybutane (DEB) testing for Fanconi anemia (abnormal in 2 of the 14 patients tested). One patient had exome sequencing studies, but no candidate gene was identified. Various anomalies were associated with EA, and overall a genetic variant could be identified in 7 of the 33 patients tested. Chromosomal studies such as aCGH and chromosomal breakage studies should be considered, and their yield varied between 7 and 14%. Other genetic investigations such as exome sequencing could possibly have even higher yields but will need to be assessed in a large cohort. Improved genetic diagnoses in EA may improve the management of these patients by directing specific surveillance and management schemes.

Interest in using individual differences in face recognition ability to better understand the perceptual and cognitive mechanisms supporting face processing has grown substantially in recent years. The goal of this study was to determine how varying levels of face recognition ability are linked to changes in visual information extraction strategies in an identity recognition task. To address this question, fifty participants completed six tasks measuring face and object processing abilities. Using the Bubbles method (Gosselin & Schyns, 2001), we also measured each individual's use of visual information in face recognition. At the group level, our results replicate previous findings demonstrating the importance of the eye region for face identification. More importantly, we show that face processing ability is related to a systematic increase in the use of the eye area, especially the left eye from the observer's perspective. Indeed, our results suggest that the use of this region accounts for approximately 20% of the variance in face processing ability. These results support the idea that individual differences in face processing are at least partially related to the perceptual extraction strategy used during face identification.

A pilot population-based carrier screening program started in 2010 in the Saguenay-Lac-Saint-Jean region of Quebec, Canada, for four recessive diseases with local founder effects (tyrosinemia type I, autosomal recessive spastic ataxia of Charlevoix-Saguenay, congenital lactic acidosis, and Andermann syndrome).The objective of this study was to describe the experience of carrier couples identified through this program.Semi-structured interviews were performed with carrier couples. Thematic analysis of interview transcripts was performed to identify emerging themes.Interviews were performed with 15 carrier couples (56% response rate). Carrier couples had little knowledge about the target diseases before being identified as carriers, despite pre-test education sessions. The main motivation for screening was a recommendation by a peer who had been screened, even for those with a positive family history of one of the target conditions. Couples perceived themselves at low risk of being a carrier couple, whatever their family history. Being found to be a carrier couple was initially a shock, illustrating how ill prepared they were for such a result, but carrier couples appreciated knowing their status.Our results emphasize the informational needs of couples to make informed decisions and the importance of post-test counseling for those with positive results. Our findings can inform counseling procedures in expanded carrier screening. © 2017 John WileySons, Ltd.