Here I present: “Proteus Syndrome”, Victor McKusick, Mendelian Inheritance in Man’, 1966. icd10=Q87.3
INTRODUCTION. Proteus syndrome is a highly variable, severe disorder of asymmetric and disproportionate overgrowth of body parts, connective tissue nevi, epidermal nevi, dysregulated adipose tissue, and vascular malformations. Specific features include cerebriform connective tissue nevus, thin limbs, lipomas, and lung cysts. Some patients may have intellectual disability with face dysmorphia. Deep venous thrombosis is common and constitutes a significant risk factor. Many features of Proteus syndrome overlap with other overgrowth syndromes.
ATM serine/threonine kinase (ataxia-telangiectasia mutated is abbreviation symbol ATM) is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks (canonical pathway), oxidative stress, topoisomerase cleavage complexes, splicing intermediates, R-loops and in some cases by single-strand DNA breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint, leading to cell cycle arrest, DNA repair or apoptosis.
There is evidence that Proteus syndrome is associated with mosaicism for a somatic activating mutation in the AKT1 gene. The name type-1 AKT does not refer to its function. The “AK” in AKT refers to the AKR mouse strain that develops spontaneous thymic lymphomas. The “T” stands for “thymoma” the letter was added when a transforming retrovirus was isolated from the AJ mouse strain, which was termed “AKT“.
The AKT1 gene is on cytogenetic location 14q32.3 and genomic coordinates 14:104,769,349-104,795,748. The screenshot of the AKT1 gene bp (base pairs) of DNA sequence length is shown BELOW. Nine (9) other genes besides AKT1 in the 14q32.3 cytogenetic location are listed BENEATH.
| Coordinate | Symbol | Genomic Name |
| 14:104,579,764 | C14orf180 | Chromosome 14 open reading frame 180 |
| 14:104,681,133 | INF2 | Inverted formin 2 |
| 14:104,724,229 | ADSS1 | Adenylosuccinate synthase 1 |
| 14:104,753,147 | SIVA1 | SIVA apoptosis-inducing factor 1 |
| 14:104,769,349 | AKT1 | AKT serine/threonine kinase |
| 14:104,800,554 | ZBTB42 | Zinc finger- and BTB domain-containing protein 42 |
| 14:104,864,513 | CEP170B | Centrosomal protein 170B |
| 14:104,924,879 | PLD4 | Phospholipase D family, member 4 |
| 14:104,937,253 | AHNAK2 | AHNAK nucleoprotein 2 |
| 14:105,009,573 | CDCA4 | Cell division cycle-associated protein 4 |
