Find out the predicted most haploinsufficient genes (those with the top percentile score or the most red in the list). Among the most haploinsufficient genes, identify those that appear to have an entry in OMIM and OMIM morbid.
For patient 135 a total of four genes are predicted as likely haploinsufficient: MEF2C, CETN3, RASA1, and CCNH. Note that a number of them appear blank, i.e., no haploinsufficiency score is available for those genes. In DECIPHER, OMIM and OMIM morbid genes are a subset of the official HGNC gene list. OMIM morbid, in particular, is the most useful from a clinical perspective because it is a catalogue of known disease genes. When clicking on any gene name, a new window appears with its corresponding entry in its source database.
GPR98, MEF2C, and RASA1 appear to be the only genes among the ten affected in patient 135 that have been listed as disease-causing genes in OMIM morbid (Fig. 8.14.9). MEF2C has recently been shown to be the critical gene underlying the 5q14.3q15 microdeletion syndrome (Jaillard et al., 2010; Le Meur et al., 2010; Zweier et al., 2010) giving rise to severe mental retardation, seizure disorders, and a common set of facial features.
Figure 8.14.9. GPR98, MEF2C, and RASA1 are identified as disease causing by OMIM Morbid among the list of overlapping genes in the 5:86170311-90103610 region.