Investigating the impact of screen-sharing visual aids during genomic results disclosure via telehealth in diverse families in the TeleKidSeq pilot study.

Purpose: Telehealth genetic counseling is comparable to in-person visits in terms of satisfaction, knowledge, and psychological outcomes, but using visual aids can be challenging on telehealth platforms. This pilot study assessed if the "screen-sharing" feature via Zoom to display visual aids during results disclosure session positively impacted parental experience and comprehension of their child's genomic results especially in underrepresented groups and those with limited English proficiency.

Methods: In the TeleKidSeq pilot study, 409 children with suspected genetic conditions underwent genome sequencing.

Genomic ascertainment to quantify prevalence and cancer risk in adults with pathogenic and likely pathogenic germline variants in RASopathy genes.

Purpose: Genomic ascertainment of electronic health record-linked exome data in two large biobanks was used to quantify germline pathogenic/likely pathogenic (P/LP) variant prevalence, cancer prevalence, and survival in adults with non- RAS/mitogen-activated protein kinase genes (RASopathies).

Patients And Methods: Germline RASopathy variants were examined from adult participants in UK Biobank (UKBB; n=469,802), Geisinger MyCode (n=167,050) and Mount Sinai Bio (n=30,470). Variants were classified as per American College of Medical Genetics/Association for Molecular Pathology criteria and reviewed by a RASopathy variant expert.

Hospitalization and Hospitalized Delirium Are Associated With Decreased Access to Kidney Transplantation and Increased Risk of Waitlist Mortality.

Background: Kidney transplant (KT) candidates often experience hospitalizations, increasing their delirium risk. Hospitalizations and delirium are associated with worse post-KT outcomes, yet their relationship with pre-KT outcomes is less clear. Pre-KT delirium may worsen access to KT due to its negative impact on cognition and ability to maintain overall health.

Molecular Signature Associated With Acute Rejection in Vascularized Composite Allotransplantation.

Background: A deeper understanding of acute rejection in vascularized composite allotransplantation is paramount for expanding its utility and longevity. There remains a need to develop more precise and accurate tools for diagnosis and prognosis of these allografts, as well as alternatives to traditional immunosuppressive regimens.

Methods: Twenty-seven skin biopsies collected from 3 vascularized composite allotransplantation recipients, consisting of face and hand transplants, were evaluated by histology, immunohistochemistry staining, and gene expression profiling.

An Update on the Survival of the First 50 Face Transplants Worldwide.

Importance: Since 2005, a total of 50 face transplants have been reported from 18 centers in 11 countries. The overall survival of the grafts has not yet been established.

Objective: To assess the survival of the face transplant grafts and evaluate factors potentially influencing it.

The BabySeq Project: A clinical trial of genome sequencing in a diverse cohort of infants.

Efforts to implement and evaluate genome sequencing (GS) as a screening tool for newborns and infants are expanding worldwide. The first iteration of the BabySeq Project (2015-2019), a randomized controlled trial of newborn sequencing, produced novel evidence on medical, behavioral, and economic outcomes. The second iteration of BabySeq, which began participant recruitment in January 2023, examines GS outcomes in a larger, more diverse cohort of more than 500 infants up to one year of age recruited from pediatric clinics at several sites across the United States.

Trisomy 21 and Congenital Heart Disease: Impact on Health and Functional Outcomes From Birth Through Adolescence: A Scientific Statement From the American Heart Association.

Due to improvements in recognition and management of their multisystem disease, the long-term survival of infants, children, and adolescents with trisomy 21 and congenital heart disease now matches children with congenital heart disease and no genetic condition in many scenarios. Although this improved survival is a triumph, individuals with trisomy 21 and congenital heart disease have unique and complex care needs in the domains of physical, developmental, and psychosocial health, which affect functional status and quality of life. Pulmonary hypertension and single ventricle heart disease are 2 known cardiovascular conditions that reduce life expectancy in individuals with trisomy 21.

Combined Whole Eye and Face Transplant: Microsurgical Strategy and 1-Year Clinical Course.

Importance: Catastrophic facial injury with globe loss remains a formidable clinical problem with no previous reports of reconstruction by whole eye or combined whole eye and facial transplant.

Objective: To develop a microsurgical strategy for combined whole eye and facial transplant and describe the clinical findings during the first year following transplant.

Design, Setting, And Participant: A 46-year-old man who sustained a high-voltage electrical injury with catastrophic tissue loss to his face and left globe underwent combined whole eye and face transplant using personalized surgical devices and a novel microsurgical strategy at a specialized center for vascularized composite allotransplantation.

Sudden Death in Pediatric Patient With Dilated Cardiomyopathy Due to Founder Variant in : Case Report.

The gene encodes a transcription factor that plays a role in atrioventricular nodal and myocardial development. Pathogenic variants of are associated with congenital heart disease and sudden cardiac death. The missense variant in this case is one of the more common ones in Northern Europe and has high penetrance in familial cases.

Evaluating parental personal utility of pediatric genetic and genomic testing in a diverse, multilingual population.

There is increasing evidence of the clinical utility of genetic and genomic testing (GT); however, factors influencing personal utility of GT, especially in diverse, multilingual populations, remain unclear. We explored these factors in a diverse cohort of parents/guardians (participants) whose children received clinical GT through the NYCKidSeq program. A total of 847 participants completed surveys at baseline, post-results disclosure, and 6 months (6m) post-results.

Physician and informal care use explained by the Pediatric Quality of Life Inventory (PedsQL) in children with suspected genetic disorders.

Purpose: To examine associations between Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and PedsQL Infant Scales with formal health care resource utilization (HCRU) and informal caregiver burden.

Methods: We studied a pediatric cohort of 837 patients (median age: 8.

Automated Identification of Germline Mutations in Family Trios: A Consensus-Based Informatic Approach.

Accurate identification of germline variants (DNVs) remains a challenging problem despite rapid advances in sequencing technologies as well as methods for the analysis of the data they generate, with putative solutions often involving filters and visual inspection of identified variants. Here, we present a purely informatic method for the identification of DNVs by analyzing short-read genome sequencing data from proband-parent trios. Our method evaluates variant calls generated by three genome sequence analysis pipelines utilizing different algorithms-GATK HaplotypeCaller, DeepTrio and Velsera GRAF-exploring the assumption that a requirement of consensus can serve as an effective filter for high-quality DNVs.

NPSV-deep: a deep learning method for genotyping structural variants in short read genome sequencing data.

Motivation: Structural variants (SVs) play a causal role in numerous diseases but can be difficult to detect and accurately genotype (determine zygosity) with short-read genome sequencing data (SRS). Improving SV genotyping accuracy in SRS data, particularly for the many SVs first detected with long-read sequencing, will improve our understanding of genetic variation.

Results: NPSV-deep is a deep learning-based approach for genotyping previously reported insertion and deletion SVs that recasts this task as an image similarity problem.

-Mutant Cardiomyocyte Model of Multifocal Atrial Tachycardia.

Background: Germline gain-of-function pathogenic variants cause Costello syndrome (CS). During early childhood, 50% of patients develop multifocal atrial tachycardia, a treatment-resistant tachyarrhythmia of unknown pathogenesis. This study investigated how overactive HRAS activity triggers arrhythmogenesis in atrial-like cardiomyocytes (ACMs) derived from human-induced pluripotent stem cells bearing CS-associated variants.

Functional dissection of human cardiac enhancers and noncoding de novo variants in congenital heart disease.

Rare coding mutations cause ∼45% of congenital heart disease (CHD). Noncoding mutations that perturb cis-regulatory elements (CREs) likely contribute to the remaining cases, but their identification has been problematic. Using a lentiviral massively parallel reporter assay (lentiMPRA) in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), we functionally evaluated 6,590 noncoding de novo variants (ncDNVs) prioritized from the whole-genome sequencing of 750 CHD trios.