Monocyte Anisocytosis Can Discriminate Between Sepsis and Sterile Inflammation, but not Mortality, in Critically Ill Surgical/Trauma Patients: A Secondary Prospective Analysis.

Objectives Background: Monocyte anisocytosis (monocyte distribution width [MDW]) has been previously validated to predict sepsis and outcome in patients presenting in the emergency department and mixed-population ICUs. Determining sepsis in a critically ill surgical/trauma population is often difficult due to concomitant inflammation and stress. We examined whether MDW could identify sepsis among patients admitted to a surgical/trauma ICU and predict clinical outcome.

Optical Genome Mapping: A New Tool for Cytogenomic Analysis.

Optical genome mapping (OGM) has recently emerged as a new technology in the clinical cytogenomics laboratories. This methodology has the ability to detect balanced and unbalanced structural rearrangements using ultra-high molecular weight DNA. This article discusses the uses of this new technology in both constitutional and somatic settings, its advantages as well as opportunity for improvements.

Two MLN-TK patients with ETV::ABL1 fusions mediated by different mechanisms with false negative FISH results resolved with RNA fusion analysis.

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusions (MLN-TK) is a newly added entity in the World Health Organization (WHO) 5 Edition, and within this category, ETV6::ABL1 gene fusions are the most commonly reported in the literature. While patients may respond favorably to tyrosine kinase inhibitor (TKI) therapy, prognosis is generally less favorable than for BCR::ABL1-positive chronic myelogenous leukemia (CML), also treated with tyrosine kinase inhibitor therapy (TKIs). We report two patients diagnosed with MLN-TK, both of whom were positive for ETV6::ABL1 gene fusions, albeit by different mechanisms but with the same breakpoints.

Reconciling competencies in undergraduate medical genetics education: APHMG versus PCME competencies.

Purpose: We wanted to understand whether there were gaps within and/or between the Association of Professors of Human and Medical Genetics (APHMG) and the Association of Pathology Chairs (APC) published competencies for undergraduate medical education pertaining to topics in medical and/or laboratory genetics.

Methods: This study compared and contrasted the APHMG and APC competencies related to genetics to identify gaps between and within each to inform the closure of those gaps in undergraduate medical education curriculum development for medical and laboratory genetics at the University of Florida.

Results: Gaps were identified within and between both documents, many relating to neoplasia for nonheritable cancers and various topics related to laboratory genetics, such as interpretation of results, principles of laboratory diagnostics, and explaining results to others.

Systemic EBV+ T-Cell Lymphoma of Childhood with Hemophagocytic Lymphohistiocytosis in a Patient with a Highly Complex Karyotype.

Background/objective: Epstein-Barr Virus (EBV) infection can be associated with lymphocytic hematological malignancies, including systemic Epstein-Barr virus-positive T-cell lymphoma of childhood (SEBVTCL). A common complication of EBV infection, hemophagocytic lymphohistiocytosis (HLH), is a life-threatening condition of immune activation present in virtually all cases of SEBVTCL that requires urgent treatment, as this malignancy can be rapidly fatal. Abnormal karyotypes have been strongly associated with SEBVTCL as a distinguishing feature from HLH in the literature.

Severe aplastic anemia with acquired X chromosome clonality as a sole abnormality.

This case is a rare presentation of severe aplastic anemia in a 31-year-old male with acquired clonality of the X chromosome as the sole cytogenetic abnormality. This abnormality has not been reported to our knowledge, and the significance of this finding remains unclear. Comprehensive diagnostic workup included bone marrow biopsy, cytogenetic analysis, and Next-Generation sequencing, which revealed no tier I/II variants typically associated with clonal hematopoietic disorders.

Multidisciplinary analysis of pediatric T-ALL: 9q34 gene fusions.

T-cell acute lymphoblastic leukemia (T-ALL) is not as frequently reported as the B-cell counterpart (B-ALL), only occurring in about 15% of pediatric cases with a typically heterogeneous etiology. Approximately 8% of childhood T-ALL cases have rearrangements involving the ABL1 tyrosine kinase gene at 9q34.12; although a t(9;22), resulting in a fusion of ABL1 with the BCR gene at 22q11.

Are all chromosome microarrays the same? What clinicians need to know.

Microarray testing is the recommended first-tier diagnostic test for women who undergo invasive prenatal diagnostic procedures. It is well-established that microarray analysis provides information regarding copy number for changes (or copy number variants, CNVs) that may be below the resolution level of standard chromosome analysis, and that such CNVs are not related to maternal age. What may not be appreciated by ordering providers, however, are the technical differences among laboratories with respect to the established laboratory cutoff values for reporting, the definition of targeted versus nontargeted regions, and how these differences may affect the interpretation and reporting of findings which, in turn, affects counseling and possible follow-up testing of family members.

Features of Feingold syndrome 1 dominate in subjects with 2p deletions including MYCN.

Interstitial deletions of the distal short arm of chromosome 2 including MYCN have only been reported for a small number of individuals. Germline deletions and mutations of MYCN cause Feingold syndrome 1 (FS1), a rare disorder characterized by microcephaly, digit anomalies, gastrointestinal atresias, short stature, dysmorphic features, and intellectual disability. We present a series of six individuals referred for SNP microarray with overlapping deletions of 2p ranging from 3.

Constitutional Chromoanagenesis of Distal 13q in a Young Adult with Recurrent Strokes.

Constitutional chromoanagenesis events, which include chromoanasynthesis and chromothripsis and result in highly complex rearrangements, have been reported for only a few individuals. While rare, these phenomena have likely been underestimated in a constitutional setting as technologies that can accurately detect such complexity are relatively new to the mature field of clinical cytogenetics. G-banding is not likely to accurately identify chromoanasynthesis or chromothripsis, since the banding patterns of chromosomes are likely to be misidentified or oversimplified due to a much lower resolution.

Section E6.1-6.4 of the ACMG technical standards and guidelines: chromosome studies of neoplastic blood and bone marrow-acquired chromosomal abnormalities.

These American College of Medical Genetics and Genomics standards and guidelines are developed primarily as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to these standards and guidelines is voluntary and does not necessarily ensure a successful medical outcome. These standards and guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results.

22q11.21 Deletion Syndromes: A Review of Proximal, Central, and Distal Deletions and Their Associated Features.

Chromosome 22q11.21 contains a cluster of low-copy repeats (LCRs), referred to as LCR22A-H, that mediate meiotic non-allelic homologous recombination, resulting in either deletion or duplication of various intervals in the region. The deletion of the DiGeorge/velocardiofacial syndrome interval LCR22A-D is the most common recurrent microdeletion in humans, with an estimated incidence of ∼1:4,000 births.

Recurrent deletions and duplications of chromosome 2q11.2 and 2q13 are associated with variable outcomes.

Copy number variation (CNV) in the long arm of chromosome 2 has been implicated in developmental delay (DD), intellectual disability (ID), autism spectrum disorder (ASD), congenital anomalies, and psychiatric disorders. Here we describe 14 new subjects with recurrent deletions and duplications of chromosome 2q11.2, 2q13, and 2q11.

Partial monosomy of 11q22.2q22.3 including the SDHD gene in individuals with developmental delay.

Deletions in the middle portion of 11q are not as well described in the literature as terminal 11q deletions that result in Jacobsen syndrome. One confounding factor in the older literature is that the G-banding pattern of 11q13q21 is very similar to 11q21q23. The advent of fluorescence in situ hybridization and later microarray technologies have allowed for a better resolution of many of these deletions, but genotype-phenotype correlations are still difficult since these deletions are rare events.

Variable levels of tissue mosaicism can confound the interpretation of chromosomal microarray results from peripheral blood.

Chromosomal microarray analysis (CMA) has significantly increased the ability to diagnose medical conditions caused by copy-number variation in the human genome. Given that the regions involved in copy-number abnormalities often encompass multiple genes, it has been common practice in recent years to compare the phenotypes of individuals with specific copy-number alterations identified by CMA, with the goal of identifying the critical regions for particular elements of a disease phenotype. It is rarely mentioned that this practice relies heavily on the assumption that the absence of mosaicism on CMA from a peripheral blood sample (the most common source of DNA in current clinical practice) reflects the absence of mosaicism in other tissues.

The recurrent distal 22q11.2 microdeletions are often de novo and do not represent a single clinical entity: a proposed categorization system.

Purpose: The five segmental duplications (LCR22-D to -H) at the distal region of chromosome 22 band q11.2 in the region immediately distal to the DiGeorge/velocardiofacial syndrome deleted region have been implicated in the recurrent distal 22q11.2 microdeletions.

Complex chromosome rearrangement of 6p25.3->p23 and 12q24.32->qter in a child with moyamoya.

A 7-year-old white girl presented with left hemiparesis and ischemic stroke secondary to moyamoya syndrome, a progressive cerebrovascular occlusive disorder of uncertain but likely multifactorial etiology. Past medical history revealed hearing loss and developmental delay/intellectual disability. Routine karyotype demonstrated extra chromosomal material on 6p.

Prenatal diagnosis of two fetuses with deletions of 8p23.1, critical region for congenital diaphragmatic hernia and heart defects.

Microdeletions of 8p23.1 are mediated by low copy repeats and can cause congenital diaphragmatic hernia (CDH) and cardiac defects. Within this region, point mutations of the GATA4 gene have been shown to cause cardiac defects.

Three cases of isolated terminal deletion of chromosome 8p without heart defects presenting with a mild phenotype.

Individuals with isolated terminal deletions of 8p have been well described in the literature, however, molecular characterization, particularly by microarray, of the deletion in most instances is lacking. The phenotype of such individuals falls primarily into two categories: those with cardiac defects, and those without. The architecture of 8p has been demonstrated to contain two inversely oriented segmental duplications at 8p23.

UPD detection using homozygosity profiling with a SNP genotyping microarray.

Single nucleotide polymorphism (SNP) based chromosome microarrays provide both a high-density whole genome analysis of copy number and genotype. In the past 21 months we have analyzed over 13,000 samples primarily referred for developmental delay using the Affymetrix SNP/CN 6.0 version array platform.

Microdeletion/microduplication of proximal 15q11.2 between BP1 and BP2: a susceptibility region for neurological dysfunction including developmental and language delay.

The proximal long arm of chromosome 15 has segmental duplications located at breakpoints BP1-BP5 that mediate the generation of NAHR-related microdeletions and microduplications. The classical Prader-Willi/Angelman syndrome deletion is flanked by either of the proximal BP1 or BP2 breakpoints and the distal BP3 breakpoint. The larger Type I deletions are flanked by BP1 and BP3 in both Prader-Willi and Angelman syndrome subjects.

Molecular cytogenetic characterization of two cases with constitutional distal 11q duplication/triplication.

Here, we report two cases with isolated distal 11q rearrangement and multiple congenital anomalies. The first patient is a two-and-a-half year old male referred to our genetics clinic due to dysmorphic features and developmental delay including speech delay. Using conventional and molecular cytogenetic techniques, we demonstrate that he carries a recombinant chromosome with duplication of the 11q23.