Genome Mapping Nomenclature.

Background: Genome Mapping Technologies (optical and electronic) use ultra-high molecular weight DNA to detect structural variation and have application in constitutional genetic disorders, hematological neoplasms, and solid tumors. Genome mapping can detect balanced and unbalanced structural variation, copy number changes, and haplotypes. The technique is analogous to chromosomal microarray analysis, although genome mapping has the added benefit of being able to detect and ascertain the nature of more abnormalities in a single assay than array, karyotyping, or FISH alone.

Addenda to ISCN 2020.

Since the publication of ISCN 2020, the ISCN Standing Committee have noted some clarification of the text and additional examples were needed. These addenda have already been published online (https://iscn.karger.

Porokeratotic eccrine ostial and dermal duct nevus associated with an 11 megabase 3p deletion.

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare eccrine hamartoma; the etiology is incompletely understood. A patient presented with congenital, widespread PEODDN. Clinical assessment, histopathologic, cytogenetic, and molecular genetic investigations on affected cells were pursued.

ALU transposition induces familial hypertrophic cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy (LVH) in the absence of predisposing cardiovascular conditions. Pathogenic variants in at least 16 cardiac sarcomeric genes have been implicated in HCM, most of which act in a dominant-negative fashion. However loss-of-function (haploinsufficiency) is the most common disease mechanism for pathogenic variants in MYBPC3, suggesting that MYBPC3 complete deletion may play a role in HCM pathogenesis.

Adopting High-Resolution Allele Frequencies Substantially Expedites Variant Interpretation in Genetic Diagnostic Laboratories.

A cohort of 1242 individuals tested in a clinical diagnostic laboratory was used to test whether the filtering allele frequencies (FAFs)-based framework, recently recommended for MHY7-associated cardiomyopathy, is extendable to 45 cardiomyopathy genes. Statistical analysis revealed a threshold of 0.00164% for the extreme outlier allele frequencies (AFs), based on the Genome Aggregation Database (exome fraction) total AFs of 138 unique pathogenic and likely pathogenic variants; 135 of them (97.

Genetic Diagnostic Testing for Inherited Cardiomyopathies: Considerations for Offering Multi-Gene Tests in a Health Care Setting.

Inherited cardiomyopathies (ICs) are a major cause of heart disease. Given their marked clinical and genetic heterogeneity, the content and clinical utility of IC multi-gene panels has been the topic of continuous debate. Our genetics diagnostic laboratory has been providing clinical diagnostic testing for ICs since 2012.

Atypical Hepatic Mesenchymal Hamartoma: Histologic Appearance, Immunophenotype, and Molecular Findings.

Hepatic mesenchymal hamartoma is a rare benign neoplasm principally encountered in young children. Its origin is unknown. We report an unusual hepatic mesenchymal hamartoma in a 7-month-old girl, including histopathologic findings, immunophenotype, and karyotype.

Leveraging the power of new molecular technologies in the clinical setting requires unprecedented awareness of limitations and drawbacks: experience of one diagnostic laboratory.

Background: Advances in molecular technologies and in-silico variant prediction tools offer wide-ranging opportunities in diagnostic settings, yet they also present with significant limitations.

Objective: Here, we contextualise the limitations of next-generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA) and in-silico prediction tools routinely used by diagnostic laboratories by reviewing specific experiences from our diagnostic laboratory.

Methods: We investigated discordant annotations and/or incorrect variant 'callings' in exons of 56 genes constituting our cardiomyopathy and connective tissue disorder NGS panels.

Correction to: Use of multicolor fluorescence in situ hybridization to detect deletions in clinical tissue sections.

Figure 2 is incorrect in the original version of this article. The correct figure 2 is provided below.

Use of multicolor fluorescence in situ hybridization to detect deletions in clinical tissue sections.

A variety of laboratory methods are available for the detection of deletions of tumor suppressor genes and losses of their proteins. The clinical utility of fluorescence in situ hybridization (FISH) for the identification of deletions of tumor suppressor genes has previously been limited by difficulties in the interpretation of FISH signal patterns. The first deletion FISH assays using formalin-fixed paraffin-embedded tissue sections had to deal with a significant background level of signal losses affecting nuclei that are truncated by the cutting process of slide preparation.

Reinterpretation of sequence variants: one diagnostic laboratory's experience, and the need for standard guidelines.

PurposeThe advent of next-generation sequencing resulted in substantial increases in the number of variants detected, interpreted, and reported by molecular genetics diagnostic laboratories. Recent publications have provided standards for the interpretation of sequence variants, but there are currently no standards regarding reinterpretation of these variants. Recognizing that significant changes in variant classification may occur over time, many genetics diagnostic laboratories have independently developed practices for variant reinterpretation.

A rare case of pediatric lipoma with t(9;12)(p22;q14) and evidence of HMGA2-NFIB gene fusion.

Lipoma is a benign tumor, typically of adulthood, with characteristic cytogenetic findings, including rearrangement of 12q13-15; these rearrangements often lead to the fusion of the HMGA2 gene at this locus to the transcriptional regulatory domain of its fusion partner, resulting in neomorphic activity that presumably facilitates the neoplastic process. Herein, we report a rare case of pediatric lipoma with t(9;12)(p22;q14) and evidence of HMGA2-NFIB gene fusion in a 9 year-old boy. This case provides further evidence of the link between NFIB rearrangement and early-onset, deep-seated lipomatous tumors.

Variable developmental delays and characteristic facial features-A novel 7p22.3p22.2 microdeletion syndrome?

Isolated 7p22.3p22.2 deletions are rarely described with only two reports in the literature.

Update on molecular findings in rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumour in children and adolescents. Histologically RMS resembles developing fetal striated skeletal muscle. RMS is stratified into different histological subtypes which appear to influence management plans and patient outcome.

HGVS Recommendations for the Description of Sequence Variants: 2016 Update.

The consistent and unambiguous description of sequence variants is essential to report and exchange information on the analysis of a genome. In particular, DNA diagnostics critically depends on accurate and standardized description and sharing of the variants detected. The sequence variant nomenclature system proposed in 2000 by the Human Genome Variation Society has been widely adopted and has developed into an internationally accepted standard.

Genotype-phenotype characterization in 13 individuals with chromosome Xp11.22 duplications.

We report 13 new individuals with duplications in Xp11.22-p11.23.

Severe craniosynostosis in an infant with deletion 22q11.2 syndrome.

We report a male infant with 22q11.2 deletion syndrome and very severe multi-sutural craniosynostosis associated with increased intracranial pressure, marked displacement of brain structures, and extensive erosion of the skull. While uni- or bi-sultural craniosynostosis is a recognized (though relatively uncommon) feature of 22q11 deletion syndrome, a severe multi-sutural presentation of this nature has never been reported.

Nablus mask-like facial syndrome: deletion of chromosome 8q22.1 is necessary but not sufficient to cause the phenotype.

Nablus mask-like facial syndrome (NMLFS) has many distinctive phenotypic features, particularly tight glistening skin with reduced facial expression, blepharophimosis, telecanthus, bulky nasal tip, abnormal external ear architecture, upswept frontal hairline, and sparse eyebrows. Over the last few years, several individuals with NMLFS have been reported to have a microdeletion of 8q21.3q22.

Novel clinical findings in a case of postnatally diagnosed trisomy 12 mosaicism.

We report on a girl with trisomy 12 mosaicism diagnosed postnatally. She has been followed from 4 months of age for developmental delay, unilateral sensorineural hearing loss, intestinal malrotation, hemi-hyperplasia, pigmentary dysplasia, retinopathy, and a vascular ring. To our knowledge, there have been no reports of complete trisomy 12 in the literature.

Apparent transmission distortion of a pericentric chromosome one inversion in a large multi-generation pedigree.

Pericentric chromosome inversions are often associated with infertility, recurrent pregnancy loss, and an increased risk for offspring with congenital anomalies. We report on a chromosome 1 inversion between 1p36.21 and 1q42.

Canadian College of Medical Geneticists guidelines for the indications, analysis, and reporting of cancer specimens.

The Canadian College of Medical Geneticists (ccmg) is a national organization of medical and laboratory geneticists. The mission of the ccmg is to establish and maintain high-quality professional and ethical standards for medical genetics services in Canada and to help to ensure that service of the highest quality is delivered to the Canadian public.Cancer cytogenetics is one of the sections of practice of the ccmg.

HLA-DR(negative), CD34(negative) hypergranular acute myeloid leukemia with trisomy 6 and del(5)(q22q33): case report and review of the literature.

We report a unique pediatric case of hypergranular acute myeloid leukemia with myelodysplasia-related changes. The patient presented with moderate leukocytosis with neutrophilia with left-shift maturation and dysplasia, anemia, and multiple sclerotic bone lesions. The bone marrow was hypercellular with a predominance of myeloblast cells and/or abnormal promyelocytes with hypergranular cytoplasm.