These cells produce a large amount of proteins from a small amount of precursors and so are constantly working and under a reasonable amount of stress. So with a mutation in eIF2B, slight increases in the amount of stress these cells encounter occur, making them more susceptible to failure due to stress. The large amount of oligodendrocytes which display apoptotic characteristics and express apoptotic proteins suggests cell number reduction in the early stages of the disease. Premature ovarian failure has also been associated with diminishing white matter. However through an intensive survey, it was determined that even if an individual has premature ovarian failure, she does not necessarily have VWM. eIF2Bs role
eIF2B is the guanine nucleotide-exchange factor for eIF2, and is composed of 5 subunits. The largest subunit, eIF2B5 contains the most mutations for VWM. eIF2B is a complex which is very involved with the regulation of in the translation of mRNA into proteins. eIF2B is essential for the exchange of guanosine diphosphate(GDP) for guanosine-5-triphosphate(GTP) in the initiation of translation via eIF2, because eIF2 is regenerated through this exchange. A decrease in eIF2B activity has been correlated with the onset of VWM. A common factor among VWM patients is mutations in the five subunits of eIF2B (21 discovered thus far), expressed in over 60% of the patients. These mutations lead to the decreased activity of eIF2B. The most common mutation is R113H, which is the mutation of histidine to arginine. The homozygous form of the mutation is the least severe form.
Diagnosis
Classification
The World Health Organization (WHO) has identified three subtypes of nasopharyngeal carcinoma:
type 1: squamous cell carcinoma, typically found in older adults
type 2: non-keratinizing carcinoma
type 3: undifferentiated carcinomaType 3 is most commonly found among younger children and adolescents, with a few type 2 cases. Both type 2 and 3 have been found to be associated with elevated levels of Epstein-Barr virus titers, but not type 1. Additionally, type 2 and type 3 may be followed with an influx of inflammatory cells, including lymphocytes, plasma cells, and eosinophils, generating the term lymphoepithelioma.Nasopharyngeal carcinoma, also known as nasopharyngeal cancer, is classified as a malignant neoplasm, or cancer, arising from the mucosal epithelium of the nasopharynx, most often within the lateral nasopharyngeal recess or fossa of Rosenmüller (a recess behind the entrance of the eustachian tube opening). The World Health Organization classifies nasopharyngeal carcinoma in three types, in order of frequency: Non-keratinizing squamous cell carcinoma; keratinizing squamous cell carcinoma; and basaloid squamous cell carcinoma. The tumor must show evidence of squamous differentiation, with the non-keratinizing type (also known as lymphoepithelioma) the tumor most strongly associated with Epstein–Barr virus infection of the cancerous cells. Staging
Staging of nasopharyngeal carcinoma is based on clinical and radiologic examination. Most patients present with Stage III or IV disease. Stage I is a small tumor confined to nasopharynx. Stage II is a tumor extending in the local area, or that with any evidence of limited neck (nodal) disease. Stage III is a large tumor with or without neck disease, or a tumor with bilateral neck disease.