GCK associated with MODY 2, CCM2 associated with type 2 cerebral cavernous malformations, OGDH associated with alpha-ketoglutarate dehydrogenase deficiency (short stature, cognitive impairment, and movement abnormalities), and IGFBP-3 whose deletion has been associated with a 20% decrease in postnatal growth are among these genes (3).
To summarize, our patient with hyperglycemia and dysmorphic features had a deletion of 7.23 Mb comprising the region 7p13-p12.1, with involvement of 39 OMIM genes, including: GCK associated with MODY 2, CCM2 associated with type 2 cerebral cavernous malformations, IGFBP-3 associated with decreased postnatal growth, and OGDH associated with alpha-ketoglutarate dehydrogenase deficiency.
Genes in deleted region (7p13-p12.1) and predicted phenotypic effects Gene OMIM Description HI% pLI Phenotype number GCK 138079 Glucokinase 8.07 0.20 MODY type 2 CCM2 607929 CCM2 scaffolding 28.18 0.48 Cerebral protein cavernomatous malformations IGFBP-3 146732 Insulin-like growth 6.39 0.36 Decrease in factor-binding postnatal growth protein 3 OGDH 613022 Oxoglutarate 17.23 0.99 Short stature, dehydrogenase hypotonia, cognitive impairment, and movement abnormalities OMIM: Online Mendelian Inheritance in Man, MODY: maturity-onset diabetes of the young, HI: haploinsufficiency index - protein coding genes have been scored according to their predicted probability of exhibiting haploinsufficiency (5), pLI: lost intolerance score.
In the study conducted using mouse model, researchers isolated two distinct mutations of Ccm2.
They tested their hypothesis by administering simvastatin, which is known to inhibit Rho activity, to mouse models with the Ccm2 mutations and saw that the drugs strengthened the damaged blood vessels in the mice.