Deleterious coding variation associated with autism is consistent across populations, as exemplified by admixed Latin American populations.

The past decade has seen remarkable progress in identifying genes that, when impacted by deleterious coding variation, confer high risk for autism spectrum disorder (ASD), intellectual disability, and other developmental disorders. However, most underlying gene discovery efforts have focused on individuals of European ancestry, limiting insights into genetic risks across diverse populations. To help address this, the Genomics of Autism in Latin American Ancestries Consortium (GALA) was formed, presenting here the largest sequencing study of ASD in Latin American individuals (n>15,000).

Rehabilitation practices during hematopoietic stem cell transplantation: An international survey.

Background And Objective: Rehabilitation therapy plays an important role in treating physical and functional impairments observed in individuals undergoing hematopoietic stem cell transplants (HSCT). This study assessed the rehabilitation practices implemented in the HSCT population internationally.

Materials And Methods: A 48-question online survey comprising questions soliciting information regarding patient characteristics, therapy details (timing, indication, and administering providers), outcome measures, and precautions were developed by an international group of cancer rehabilitation physicians.

A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders.

Unsolved Mendelian cases often lack obvious pathogenic coding variants, suggesting potential non-coding etiologies. Here, we present a single cell multi-omic framework integrating embryonic mouse chromatin accessibility, histone modification, and gene expression assays to discover cranial motor neuron (cMN) cis-regulatory elements and subsequently nominate candidate non-coding variants in the congenital cranial dysinnervation disorders (CCDDs), a set of Mendelian disorders altering cMN development. We generate single cell epigenomic profiles for ~86,000 cMNs and related cell types, identifying ~250,000 accessible regulatory elements with cognate gene predictions for ~145,000 putative enhancers.

A blended genome and exome sequencing method captures genetic variation in an unbiased, high-quality, and cost-effective manner.

We deployed the Blended Genome Exome (BGE), a DNA library blending approach that generates low pass whole genome (1-4× mean depth) and deep whole exome (30-40× mean depth) data in a single sequencing run. This technology is cost-effective, empowers most genomic discoveries possible with deep whole genome sequencing, and provides an unbiased method to capture the diversity of common SNP variation across the globe. To evaluate this new technology at scale, we applied BGE to sequence >53,000 samples from the Populations Underrepresented in Mental Illness Associations Studies (PUMAS) Project, which included participants across African, African American, and Latin American populations.

Palliative Rehabilitation in Patients with Cancer: Definitions, Structures, Processes and Outcomes.

Purpose Of Review: This review examines the literature on palliative rehabilitation for patients with advanced cancer, focusing on definitions, structures, processes, and outcomes.

Recent Findings: Palliative cancer rehabilitation targets comfort and functional improvement for patients with limited rehabilitation potential across various settings. The palliative cancer rehabilitation team, typically led by a physician, coordinates symptom management and referrals to rehabilitation and other allied healthcare professionals as needed.

Onabotulinum toxin injections for shoulder and chest wall muscle pain in breast cancer survivors: retrospective study - preliminary report.

Objectives: The primary objective of this retrospective review is to describe patient-reported improvement in muscular pain after initial treatment with onabotulinum toxin. A secondary objective was to determine other physiatry (physical medicine & rehabilitation (PM&R)) interventions ordered.

Methods: Preliminary retrospective review of physiatry interventions for 47 patients referred by breast radiation oncology to PM&R at a tertiary referral-based academic cancer centre clinic from 1 January 2018 to 31 December 2021 for muscular shoulder/chest wall pain.

Expanding the genetics and phenotypes of ocular congenital cranial dysinnervation disorders.

Purpose: To identify genetic etiologies and genotype/phenotype associations for unsolved ocular congenital cranial dysinnervation disorders (oCCDDs).

Methods: We coupled phenotyping with exome or genome sequencing of 467 pedigrees with genetically unsolved oCCDDs, integrating analyses of pedigrees, human and animal model phenotypes, and variants to identify rare candidate single nucleotide variants, insertion/deletions, and structural variants disrupting protein-coding regions. Prioritized variants were classified for pathogenicity and evaluated for genotype/phenotype correlations.

Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease.

Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and, with new innovative methods, can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort of 6,633 families (15,759 individuals) with heterogeneous phenotypes and variable prior genetic testing collected at the Broad Institute Center for Mendelian Genomics of the Genomics Research to Elucidate the Genetics of Rare Diseases consortium and analyzed using the seqr platform.

Predictors of a Preference for Telemedicine Virtual Visits in Patients Undergoing Cancer Rehabilitation.

The purpose of this retrospective study was to examine the use of virtual visits (telemedicine) at our cancer rehabilitation outpatient clinics from March 2020 to August 2021, when virtual visits became more widely available, and to identify any demographic and clinical variables making patients more likely to favor virtual over in-person visits. There were 3971 outpatient encounters (2020 virtual and 1951 in-person visits from a total of 1638 patients) in our cancer rehabilitation outpatient clinics during this time frame. Significant findings in both the univariate and multivariate analyses were race ( P < 0.

Inpatient Rehabilitation of Hematopoietic Stem Cell Transplant Patients: Managing Challenging Impairments and Medical Fragility.

Hematopoietic stem cell transplants play an important role in the treatment of cancer, particularly hematologic malignancies. These patients can encounter functional impairments unique to hematopoietic stem cell transplant, including deconditioning, cancer-related fatigue, steroid myopathy, graft versus host disease, and capillary leak syndrome. Medical fragility and increased risk of infection may make rehabilitation challenging on the acute care and postacute care settings.

Unique Capabilities of Genome Sequencing for Rare Disease Diagnosis.

Background: Causal variants underlying rare disorders may remain elusive even after expansive gene panels or exome sequencing (ES). Clinicians and researchers may then turn to genome sequencing (GS), though the added value of this technique and its optimal use remain poorly defined. We therefore investigated the advantages of GS within a phenotypically diverse cohort.

A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders.

Unsolved Mendelian cases often lack obvious pathogenic coding variants, suggesting potential non-coding etiologies. Here, we present a single cell multi-omic framework integrating embryonic mouse chromatin accessibility, histone modification, and gene expression assays to discover cranial motor neuron (cMN) cis-regulatory elements and subsequently nominate candidate non-coding variants in the congenital cranial dysinnervation disorders (CCDDs), a set of Mendelian disorders altering cMN development. We generated single cell epigenomic profiles for ~86,000 cMNs and related cell types, identifying ~250,000 accessible regulatory elements with cognate gene predictions for ~145,000 putative enhancers.

Role of Outpatient Physical Medicine and Rehabilitation in a Multidisciplinary Prehabilitation Program for Older Adults Before Allogeneic Hematopoietic Stem Cell Transplant.

Introduction: Physical rehabilitation is increasingly incorporated throughout the allogeneic hematopoietic stem cell transplant journey for older adults.

Objective: This study aimed to describe physical medicine and rehabilitation-related diagnoses, exercise barriers, and management recommendations for older adults before allogeneic hematopoietic stem cell transplant.

Design: Fifty physical medicine and rehabilitation consults as part of the Enhanced Recovery-Stem Cell Transplant multidisciplinary prehabilitation program at a comprehensive cancer center were retrospectively reviewed.

Exome copy number variant detection, analysis and classification in a large cohort of families with undiagnosed rare genetic disease.

Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and with new innovative methods can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort of 6,633 families (15,759 individuals) with heterogeneous phenotypes and variable prior genetic testing collected at the Broad Institute Center for Mendelian Genomics of the GREGoR consortium.

GATK-gCNV enables the discovery of rare copy number variants from exome sequencing data.

Copy number variants (CNVs) are major contributors to genetic diversity and disease. While standardized methods, such as the genome analysis toolkit (GATK), exist for detecting short variants, technical challenges have confounded uniform large-scale CNV analyses from whole-exome sequencing (WES) data. Given the profound impact of rare and de novo coding CNVs on genome organization and human disease, we developed GATK-gCNV, a flexible algorithm to discover rare CNVs from sequencing read-depth information, complete with open-source distribution via GATK.

Changes in Patterns of Referral for Inpatient Rehabilitation Cancer Patients Due to COVID-19: A Retrospective Study.

There is a paucity of literature on the effect of COVID-19 on hospital processes. We hypothesized that COVID-19 was associated with decreased cancer physiatry referrals in 2020. This is a retrospective cohort study of consecutive patients from April to July 2019 and 2020 admitted at an academic quaternary cancer center.

Landscape of mSWI/SNF chromatin remodeling complex perturbations in neurodevelopmental disorders.

DNA sequencing-based studies of neurodevelopmental disorders (NDDs) have identified a wide range of genetic determinants. However, a comprehensive analysis of these data, in aggregate, has not to date been performed. Here, we find that genes encoding the mammalian SWI/SNF (mSWI/SNF or BAF) family of ATP-dependent chromatin remodeling protein complexes harbor the greatest number of de novo missense and protein-truncating variants among nuclear protein complexes.

Frequency, Characteristics, and Risk Factors for Falls at an Inpatient Cancer Rehabilitation Unit.

Purpose: Falls in the hospital can lead to adverse events, including injuries. Studies have shown that patients with cancer and those undergoing inpatient rehabilitation (IPR) are at higher risk for falls. Therefore, we measured the frequency, degree of harm, and characteristics of patients who fell in an inpatient cancer rehabilitation unit.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance.