Wales Infants' and childreN's Genome Service (WINGS): providing rapid genetic diagnoses for unwell children.

Introduction: This study reviews the first 3 years of delivery of the first National Health Service (NHS)-commissioned trio rapid whole genome sequencing (rWGS) service for acutely unwell infants and children in Wales.

Methods: Demographic and phenotypic data were prospectively collected as patients and their families were enrolled in the Wales Infants' and childreN's Genome Service (WINGS). These data were reviewed alongside trio rWGS results.

Börjeson-Forssman-Lehmann syndrome: delineating the clinical and allelic spectrum in 14 new families.

Börjeson-Forssman-Lehmann syndrome (BFLS) is an X-linked intellectual disability syndrome caused by variants in the PHF6 gene. We ascertained 19 individuals from 15 families with likely pathogenic or pathogenic PHF6 variants (11 males and 8 females). One family had previously been reported.

Exon-focused targeted oligonucleotide microarray design increases detection of clinically relevant variants across multiple NHS genomic centres.

In recent years, chromosomal microarrays have been widely adopted by clinical diagnostic laboratories for postnatal constitutional genome analysis and have been recommended as the first-line test for patients with intellectual disability, developmental delay, autism and/or congenital abnormalities. Traditionally, array platforms have been designed with probes evenly spaced throughout the genome and increased probe density in regions associated with specific disorders with a resolution at the level of whole genes or multiple exons. However, this level of resolution often cannot detect pathogenic intragenic deletions or duplications, which represent a significant disease-causing mechanism.