Albertine Donker

Chapter 4 194 Supplemental Figure 1. Genomic array profile of chromosome 22 of patient 1 Genomic array profile of chromosome 22 of patient 1. Profile is obtained by CytoScanHD array of Affymetrix. A . The genomic array profile of the index patient, showing a 118 kb homozygous deletion characterized by 140 array probes with a lowered 2Log(Test/Reference) ratio (red arrow). This homozygous deletion is situated in a 20.4 megabase homozygous region. The proximal breakpoint of the deletion is located at 37,374,751 Mb and the distal breakpoint at 37,492,851 Mb (breakpoints are mapped on human genome version Hg19, 2009). B . Screenshot of the UCSC genome. Here the detected deletion is indicated by the black box marked “HOMOZYGOUS DELETION” which shows that the distal breakpoint of the deletion is located between exon 2 and 3 (bold red arrow) of the TMPRSS6 gene, which is concordant with the failed sequencing efforts of exons 3-18. The distal breakpoint probably leads to nonsense-mediated decay of the messenger RNA corresponding with exon 1 and 2, resulting in the total absence of matriptase 2. The red arrow indicates the direction in which the gene is read. This screenshot also shows that besides TMPRSS6, the deletion also comprises TEX33, TST, MPST and KCTD17.