A Frame-Shift Variant Causes Neurodevelopmental and Renal Disorder Consistent with Previously Described Proximal Chromosome 19q13.11 Deletion Syndrome.

Heterozygous deletions at 19q12-q13.11 affecting TSHZ3, the teashirt zinc finger homeobox 3, have been associated with intellectual disability and behavioural issues, congenital anomalies of the kidney and urinary tract (CAKUT), and postnatal growth retardation in humans and mice. encodes a transcription factor regulating the development of neurons but is ubiquitously expressed. Using exome sequencing, we identified a heterozygous frameshift variant c.119_120dup p.Pro41SerfsTer79 in in a 7-year-old girl with intellectual disability, behavioural issues, pyelocaliceal dilatation, and mild urethral stenosis. The variant was present on the paternal TSHZ3 allele. The DNA from the father was not available for testing. This is the first report of a heterozygous point mutation in causing the same phenotype as reported for monoallelic deletions in the same region. This confirms as a novel disease gene for neurodevelopmental disorder in combination with behavioural issues and CAKUT.