Genome sequencing detects a wide range of clinically relevant copy number variants and other genomic alterations

Genet Med. 2023 Oct 20:101006. doi: 10.1016/j.gim.2023.101006. Online ahead of print. ABSTRACT PURPOSE: Copy number variants (CNVs) and other non-SNV/indel variant types contribute an important proportion of diagnoses in individuals with suspected genetic disease. This study describes the range of such variants detected by genome sequencing (GS). METHODS: For a pediatric cohort of 1032 participants […]

Cell-type-resolved somatic mosaicism reveals clonal dynamics of the human forebrain

bioRxiv. 2023 Oct 26:2023.10.24.563814. doi: 10.1101/2023.10.24.563814. Preprint. ABSTRACT Debate remains around anatomic origins of specific brain cell subtypes and lineage relationships within the human forebrain. Thus, direct observation in the mature human brain is critical for a complete understanding of the structural organization and cellular origins. Here, we utilize brain mosaic variation within specific cell […]

Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders

Brain. 2023 Nov 10:awad380. doi: 10.1093/brain/awad380. Online ahead of print. ABSTRACT The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins, and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 […]

Biallelic loss-of-function variants in WBP4, encoding a spliceosome protein, result in a variable neurodevelopmental syndrome

Am J Hum Genet. 2023 Nov 7:S0002-9297(23)00366-X. doi: 10.1016/j.ajhg.2023.10.013. Online ahead of print. ABSTRACT Over two dozen spliceosome proteins are involved in human diseases, also referred to as spliceosomopathies. WW domain-binding protein 4 (WBP4) is part of the early spliceosomal complex and has not been previously associated with human pathologies in the Online Mendelian Inheritance […]

A genetics-guided approach to the clinical management of schizophrenia

Schizophr Res. 2023 Oct 7:S0920-9964(23)00353-5. doi: 10.1016/j.schres.2023.09.042. Online ahead of print. ABSTRACT Schizophrenia is a highly heritable, severe mental illness characterized by hallucinations, delusions, social withdrawal, and cognitive dysfunction present in ∼1% of populations across cultures. There have been recent major advancements in our understanding of the genetic architecture of schizophrenia. Both rare, highly penetrant […]

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

medRxiv. 2023 Oct 5:2023.10.05.23296595. doi: 10.1101/2023.10.05.23296595. Preprint. ABSTRACT 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 […]

The Promise and Perils of Next-Generation DNA Sequencing at Birth: Proceedings of a Workshop–in Brief

National Academies of Sciences, Engineering, and Medicine. 2023. The Promise and Perils of Next-Generation DNA Sequencing at Birth: Proceedings of a Workshop–in Brief. Washington, DC: The National Academies Press. Pilot programs are employing whole genome sequencing and whole exome sequencing during the newborn phase both within the United States and internationally. While sequencing offers the […]

An approach for collaborative development of a federated biomedical knowledge graph-based question-answering system: Question-of-the-Month challenges

J Clin Transl Sci. 2023 Sep 14;7(1):e214. doi: 10.1017/cts.2023.619. eCollection 2023. ABSTRACT Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As […]

Unique Challenges of NIPT for Sex Chromosome Aneuploidy

Clin Obstet Gynecol. 2023 Sep 1;66(3):568-578. doi: 10.1097/GRF.0000000000000804. Epub 2023 Jul 24. ABSTRACT Noninvasive prenatal testing (NIPT) for the sex chromosome aneuploidies (45,X, 47,XXY, 47,XXX, and 47,XYY) differs significantly from that for the autosomal aneuploidies (trisomy 13, 18, and 21). As a group, sex chromosome aneuploidies occur more commonly (1/400) than any one isolated autosomal […]

Novel association of Dandy-Walker malformation with CAPN15 variants expands the phenotype of oculogastrointestinal neurodevelopmental syndrome

Am J Med Genet A. 2023 Aug 19. doi: 10.1002/ajmg.a.63363. Online ahead of print. ABSTRACT Oculogastrointestinal neurodevelopmental syndrome has been described in seven previously published individuals who harbor biallelic pathogenic variants in the CAPN15 gene. Biallelic missense variants have been reported to demonstrate a phenotype of eye abnormalities and developmental delay, while biallelic loss of […]

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