Respiratory disorders

Pharyngitis; Fasciitis; Necrotizing fasciitis; Centronuclear myopathy

Pharyngitis (commonly called 'sore throat') is an upper respiratory tract disease characterized by inflammation of the pharynx resulting from a bacterial, viral, or fungal infection, or from irritants such as pollutants, chemical substances, or smoking. Symptoms include pain when swallowing, enlarged tonsils covered with white discharge, cough, and fever. Necrotizing fasciitis is characterized by a severe, sudden, and rapidly spreading bacterial infection of the skin, subcutaneous tissue, and fascis. The causal bacteria gains access to the body via an external injury. Symptoms of this disease include redness and inflammation at the infection site, high fever, severe pain, swelling, blisters, and (if not treated) multiple organ failure. Centronuclear myopathy (CNM) is a muscular disease characterized by muscle weakness and an increased proportion of muscle cells with centrally located nuclei. The most common form of CNM is X-linked myotubular myopathy, which is caused by inactivating mutations in MTM1, a lipid phosphatase. Through immunofluorescence and immunoprecipitation, the SPEG protein was identified as an MTM1-interacting protein, thus implicating the protein in the pathogenesis of CNM. In addition the SPEG protein is necessary for myocyte cytoskeletal development. In muscle cells, the SPEG protein is found in a double-line that flanks the protein desmin near the Z-lines of the sarcomere and is in alignment with the terminal cisternae of the sarcoplasmic reticulum. In animal studies, mice lacking SPEG expression display abnormal myocardial development and severe cardiomyopathy. Tissue samples from the mice revealed a significantly increased proportion of muscle cells with centrally located nuclei, resembling the CNM phenotype. Therefore, loss-of-function in the SPEG protein may play a critical role in the pathogenesis of CNM.
 

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Bladder carcinomas (%CFC= -57, p<0.001); Oral squamous cell carcinomas (OSCC) (%CFC= +117, p<0.056); Ovary adenocarcinomas (%CFC= +57, p<0.039); Pituitary adenomas (ACTH-secreting) (%CFC= -45); Skin melanomas - malignant (%CFC= -69, p<0.024); Uterine fibroids (%CFC= +81, p<0.002); and Uterine leiomyomas (%CFC= -77, p<0.003). The COSMIC website notes an up-regulated expression score for SPEG in diverse human cancers of 459, which is close to the average score of 462 for the human protein kinases. The down-regulated expression score of 0 for this protein kinase in human cancers was 100% lower than average score of 60 for the human protein kinases.

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis.

Percent mutation rates per 100 amino acids length in human cancers: 0.07 % in 24773 diverse cancer specimens. This rate is only -12 % lower than the average rate of 0.075 % calculated for human protein kinases in general.

Highest percent mutation rates per 100 amino acids length in human cancers: 0.28 % in 864 skin cancers tested; 0.26 % in 1259 large intestine cancers tested; 0.24 % in 589 stomach cancers tested; 0.13 % in 603 endometrium cancers tested; 0.12 % in 1634 lung cancers tested; 0.09 % in 548 urinary tract cancers tested; 0.08 % in 238 bone cancers tested; 0.08 % in 1512 liver cancers tested; 0.06 % in 958 upper aerodigestive tract cancers tested; 0.06 % in 710 oesophagus cancers tested; 0.05 % in 1459 pancreas cancers tested; 0.04 % in 881 prostate cancers tested; 0.04 % in 833 ovary cancers tested; 0.04 % in 273 cervix cancers tested; 0.03 % in 2013 haematopoietic and lymphoid cancers tested; 0.03 % in 1305 breast cancers tested; 0.02 % in 558 thyroid cancers tested; 0.02 % in 441 autonomic ganglia cancers tested; 0.02 % in 2082 central nervous system cancers tested; 0.02 % in 1276 kidney cancers tested; 0.02 % in 127 biliary tract cancers tested; 0.01 % in 382 soft tissue cancers tested.

Most frequent mutations with the number of reports indicated in brackets: R3196Q (5); R3196* (2); R3021W (4); V2742M(3).

Twenty-nine deletions, 3 insertions, and no complex mutations are noted on the COSMIC website.