Characterization of Constitutional Ring Chromosomes over 37 Years of Experience at a Single-Site Institution.

Ring chromosomes (RCs) can be rare or common depending on the chromosome involved. With interest in the historical RCs identified by our laboratory, we curated instances to provide further information to this research field. : We carried out a retrospective, single-center study of constitutional RCs identified starting in the late 1980s.

Cytogenomic characterization of mosaic X-ring chromosomes in seventeen patients with Turner syndrome (TS)-42 years of experience at a single-site institution.

Individuals with Turner syndrome (TS) phenotypes may exhibit short stature, ovarian dysfunction, and neurocognitive disorders. Their genomes can include ring chromosomes formed from the X chromosome (RCX). Here, we present cytogenomic and clinical findings from seventeen individuals with TS who bore mosaic forms of RCX and frequently presented with short stature and concern for TS.

Clinicopathologic and Molecular Analysis of Malignant Neoplasms With Yolk Sac Tumor Differentiation in Women 40 Years of Age and Older.

Gynecologic yolk sac tumors (YSTs) are more commonly encountered in children and young women as pure or mixed germ cell tumors and are rarely observed in older women. YSTs in older women are sometimes accompanied by a Müllerian-type carcinoma component, indicating a likely somatic rather than germ-cell origin. Studies of YSTs of germ cell and somatic types in this age group are limited.

Diagnostic and Prognostic/Therapeutic Significance of Comprehensive Analysis of Bone and Soft Tissue Tumors Using Optical Genome Mapping and Next-Generation Sequencing.

Detecting somatic structural variants (SVs), copy number variants (CNVs), and mutations in bone and soft tissue tumors is essential for accurately diagnosing, treating, and prognosticating outcomes. Optical genome mapping (OGM) holds promise to yield useful data on SVs and CNVs but requires fresh or snap-frozen tissues. This study aimed to evaluate the clinical utility of data from OGM compared with current standard-of-care cytogenetic testing.

Ring Chromosomes in Hematological Malignancies Are Associated with Gene Mutations and Characteristic Copy Number Variants.

Ring chromosomes (RC) are present in <10% of patients with hematological malignancies and are associated with poor prognosis. Until now, only small cohorts of patients with hematological neoplasms and concomitant RCs have been cytogenetically characterized. Here, we performed a conventional chromosome analysis on metaphase spreads from >13,000 patients diagnosed with hematological malignancies at the Johns Hopkins University Hospital and identified 98 patients with RCs-90 with myeloid malignancies and 8 with lymphoid malignancies.

Live-born autosomal ring chromosomes at the Johns Hopkins Hospital Cytogenomics Laboratory: Case series-Spanning 52 years of experience in a single center.

Ring chromosomes (RCs) are a structural aberration that can be tolerated better in acrocentric or gonosomal chromosomes. Complete RCs arise from telomere-telomere fusions. Alternatively, genomic imbalances corresponding to the ends of the chromosomal arms can be seen with RC formation.

Complex/cryptic Gene Fusions and 1q Jumping Translocation in Pediatric Ewing Sarcomas.

Ewing sarcomas (ES) are rare small round cell sarcomas often affecting children and characterized by gene fusions involving one member of the FET family of genes (usually and a member of the ETS family of transcription factors (usually or ). The detection of rearrangements has important diagnostic value. Here, we conducted a retrospective review of 218 consecutive pediatric ES at diagnosis and found eight patients having data from chromosome analysis, FISH/microarray, and gene-fusion assay.

Recurring germline mosaicism in a family due to reversion of an inherited derivative chromosome 8 from an 8;21 translocation with interstitial telomeric sequences.

Background: Mosaicism for chromosomal structural abnormalities, other than marker or ring chromosomes, is rarely inherited.

Methods: We performed cytogenetics studies and breakpoint analyses on a family with transmission of mosaicism for a derivative chromosome 8 (der(8)), resulting from an unbalanced translocation between the long arms of chromosomes 8 and 21 over three generations.

Results: The proband and his maternal half-sister had mosaicism for a der(8) cell line leading to trisomy of the distal 21q, and both had Down syndrome phenotypic features.

Maternal stress in Shank3ex4-9 mice increases pup-directed care and alters brain white matter in male offspring.

Gene-environment interactions contribute to the risk for Autism Spectrum Disorder (ASD). Among environmental factors, prenatal exposure to stress may increase the risk for ASD. To examine if there is an interaction between exposure to maternal stress and reduced dosage or loss of Shank3, wild-type (WT), heterozygous (HET) and homozygous (HOM) female mice carrying a deletion of exons four through nine of Shank3 (Shank3ex4-9) were exposed to chronic unpredictable mild stress (CUMS) from prior to conception throughout gestation.

Interpretation of Genomic Sequencing Results in Healthy and Ill Newborns: Results from the BabySeq Project.

Genomic sequencing provides many opportunities in newborn clinical care, but the challenges of interpreting and reporting newborn genomic sequencing (nGS) results need to be addressed for its broader and effective application. The BabySeq Project is a pilot randomized clinical trial that explores the medical, behavioral, and economic impacts of nGS in well newborns and those admitted to a neonatal intensive care unit (NICU). Here we present childhood-onset and actionable adult-onset disease risk, carrier status, and pharmacogenomics findings from nGS of 159 newborns in the BabySeq Project.

Expert specification of the ACMG/AMP variant interpretation guidelines for genetic hearing loss.

Due to the high genetic heterogeneity of hearing loss (HL), current clinical testing includes sequencing large numbers of genes, which often yields a significant number of novel variants. Therefore, the standardization of variant interpretation is crucial to provide consistent and accurate diagnoses. The Hearing Loss Variant Curation Expert Panel was created within the Clinical Genome Resource to provide expert guidance for standardized genomic interpretation in the context of HL.

Reconciling newborn screening and a novel splice variant in associated with partial biotinidase deficiency: a BabySeq Project case report.

Here, we report a newborn female infant from the well-baby cohort of the BabySeq Project who was identified with compound heterozygous gene variants. The two identified variants included a well-established pathogenic variant (c.1612C>T, p.

A genome-wide screen for copy number alterations in an adolescent pilot cohort with müllerian anomalies.

Objective: To examine whether pathogenic copy number changes (CNCs) can be identified in deoxyribonucleic acid from females with different classes of müllerian anomalies.

Design: We conducted array-based copy number variant (CNV) analysis using an oligonucleotide array from deoxyribonucleic acid in 12 adolescent females with various müllerian anomalies.

Setting: University-affiliated tertiary care institution.