Identification of DIS3L2 exon 9 deletion in patients with Perlman syndrome using BAMdelbee, a novel software that enables detection of homozygous deletions in NGS data.
Genetics Institute, Soroka University Medical Center, Israel
Two affected individuals, first cousins of a large consanguinity Arab Bedouin family, presented with neonatal hypotonia, hyperechogenic kidneys, brain malformation, dysmorphism and hydrops, culminating in death in infancy. Whole exome sequencing for the two affected children and the parents of one of them could not reveal any shared homozygous pathogenic variant. BAMdelbee, generated in our lab, is a novel tool for discovering homozygous deletions in Whole-exome-sequencing (WES) and whole genome-sequencing (WGS) data. BAMdelbee locates homozygous deletions by pinpointing regions covered in all samples but the ones in question. Using BAMdelbee, we could identify a homozygous deletion of DIS3L2 exon 9 (chr2-232163250-232163750) in the two affected children. Mutations in DIS3L2 are associated with Perlman syndrome, an autosomal recessive disease. Affected children are hypotonic, with typical facial dysmorphism, renal anomalies, neurodevelopmental delay, high risk of Wilms tumor and high neonatal mortality. Loss of function mutations, including deletion of exon 9, is a known disease mechanism. We demonstrate how the BAMdelbee application can identify homozygous deletions evading detection by standard commercial software.