Germline de novo alterations of RUNX1T1 in individuals with neurodevelopmental and congenital anomalies.

Runt-related transcription factor 1 translocated to 1 (RUNX1T1; also known as eight-twenty-one [ETO]) encodes a transcription regulator for hematopoietic genes and is well known for its involvement in hematologic malignancies, particularly acute myeloid leukemia (AML). However, its role in congenital disease is less understood. This study provides detailed clinical and molecular information on three cases exhibiting neurodevelopmental and congenital anomalies with germline de novo alterations in RUNX1T1.

Synchronized long-read genome, methylome, epigenome, and transcriptome for resolving a Mendelian condition.

Resolving the molecular basis of a Mendelian condition (MC) remains challenging owing to the diverse mechanisms by which genetic variants cause disease. To address this, we developed a synchronized long-read genome, methylome, epigenome, and transcriptome sequencing approach, which enables accurate single-nucleotide, insertion-deletion, and structural variant calling and diploid genome assembly, and permits the simultaneous elucidation of haplotype-resolved CpG methylation, chromatin accessibility, and full-length transcript information in a single long-read sequencing run. Application of this approach to an Undiagnosed Diseases Network (UDN) participant with a chromosome X;13 balanced translocation of uncertain significance revealed that this translocation disrupted the functioning of four separate genes (, , , and ) previously associated with single-gene MCs.

High-dose hydroxocobalamin achieves biochemical correction and improvement of neuropsychiatric deficits in adults with late onset cobalamin C deficiency.

Cobalamin C () deficiency is the most common inborn error of intracellular cobalamin metabolism caused by pathogenic variant(s) in and manifests with methylmalonic acidemia, hyperhomocysteinemia, and hypomethioninemia with a variable age of presentation. Individuals with late-onset may be asymptomatic until manifesting neuropsychiatric symptoms, thromboembolic events, and renal disease. Although hydroxocobalamin provides a foundation for therapy, optimal dose regimen for adult patients has not been systematically evaluated.

Oral Health and Dental Clinic Attendance in Pediatric Refugees.

Dental pathology is common among refugees. The purpose of this study was to identify pediatric refugees at increased risk of caries, poor clinic attendance, and need for urgent or surgical intervention under general anesthesia. A retrospective chart review of newly arrived pediatric refugees to the United States was performed.