Detection of human cytomegalovirus cell-free DNA in pregnant women with symptomatically infected fetuses: proof-of-concept study.

Objective: To evaluate the presence and levels of cytomegalovirus (CMV) cell-free DNA (cfDNA) fragments in women pregnant with a fetus with symptomatic congenital CMV (cCMV).

Methods: The study comprised nine women whose fetuses were diagnosed with cCMV between June 2019 and July 2024 at 20 + 4 to 34 + 1 weeks' gestation (n = 8) or neonatally (n = 1) after primary or non-primary maternal infection. In eight women, cfDNA sequencing data from a single timepoint were analyzed, either retrospectively, on data generated from 11-13 weeks' gestation (n = 5) or prospectively, on data generated from 20-26 weeks' gestation (n = 3), upon the diagnosis of cCMV.

De novo and inherited dominant variants in U4 and U6 snRNAs cause retinitis pigmentosa.

The U4 small nuclear RNA (snRNA) forms a duplex with the U6 snRNA and, together with U5 and ~30 proteins, is part of the U4/U6.U5 tri-snRNP complex, located at the core of the major spliceosome. Recently, recurrent variants in the U4 RNA, transcribed from the gene, and in at least two other genes were discovered to cause neurodevelopmental disorder.

Identification of novel 3D-genome altering and complex structural variants underlying retinitis pigmentosa type 17 through a multistep and high-throughput approach.

Introduction: Autosomal dominant retinitis pigmentosa type 17 (adRP, type RP17) is caused by complex structural variants (SVs) affecting a locus on chromosome 17 (chr17q22). The SVs disrupt the 3D regulatory landscape by altering the topologically associating domain (TAD) structure of the locus, creating novel TAD structures (neo-TADs) and ectopic enhancer-gene contacts. Currently, screening for RP17-associated SVs is not included in routine diagnostics given the complexity of the variants and a lack of cost-effective detection methods.

Lipopeptide-mediated Cas9 RNP delivery: A promising broad therapeutic strategy for safely removing deep-intronic variants in .

Deep-intronic (DI) variants represent approximately 10%-12% of disease-causing genetic defects in -associated Stargardt disease (STGD1). Although many of these DI variants are amenable to antisense oligonucleotide-based splicing-modulation therapy, no treatment is currently available. These molecules are mostly variant specific, limiting their applicability to a broader patient population.

Exome variant prioritization in a large cohort of hearing-impaired individuals indicates IKZF2 to be associated with non-syndromic hearing loss and guides future research of unsolved cases.

Although more than 140 genes have been associated with non-syndromic hereditary hearing loss (HL), at least half of the cases remain unexplained in medical genetic testing. One reason is that pathogenic variants are located in 'novel' deafness genes. A variant prioritization approach was used to identify novel (candidate) genes for HL.