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According to the "Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources" (DECIPHER) (4), the 7p13-p12.1 deleted interval contains five genes (GCK, IGFBP-3, OGDH, PPIA, and PSMA2) associated with low haploinsufficiency (HI) score (HI index <10%) (5) and/or high loss intolerance score (pLI [greater than or equal to]0.9) (6) and one intermediate (CMM2: HI 28.18% and pLI 0.48).
OGDH HI is associated, according to the Human Phenotype Ontology (13), with short stature, hypotonia, cognitive impairment, and movement abnormalities, among others features.
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.
Mitochondrial impairment, and altered expression levels of key mitochondrial genes such as Ucp2 and Ogdh have been previously reported in the pancreas of first-generation adult male offspring of BPA-exposed rat dams (Wei et al.
Moreover, A[beta] disturbs the activity of several enzymes, such as pyruvate dehydrogenase (PDH) and oxoglutarate dehydrogenase (OGDH), decreasing NADH reduction, and the electron transport chain enzyme complex IV, reducing the amount of hydrogen that is translocated from the matrix to the intermembrane space (IMS), thus impairing the mitochondrial membrane potential (MMP).
confrontations, the Guinean Organization for Human Rights (OGDH)
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- Ogden Museum of Southern Art
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