Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029089 (ophthalmoplegia)
 3,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphorus magnetic resonance spectroscopic studies in bipolar disorder revealed altered brain energy metabolism resembling that of chronic progressive external ophthalmoplegia (CPEO). Mood disorder is one characteristic symptom in several families of CPEO caused by mutations of three genes, ANT1, Twinkle, and POLG. Molecular genetic analysis revealed association of bipolar disorder with mitochondrial DNA (mtDNA) 10398A polymorphism, 3644C mutation, and FDUFV2. In the postmortem brains, increased levels of mtDNA 4977bp deletion and 3243G mutation, and altered expression of mitochondria-related genes were reported. Mitochondria play an important role in neuroplasticity and apoptotic signaling via regulating intracellular calcium homeostasis. Thus, mitochondrial dysfunction may cause altered calcium homeostasis and neuroplasticity, resulting in bipolar disorder. Most molecular genetic findings in bipolar disorder regarding mitochondria and endoplasmic reticulum stress signaling are common to Parkinson's disease and diabetes mellitus. Thus, it is possible that bipolar disorder is also a disease caused by the progressive loss of some neuronal cells.
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PMID:[Mitochondrial dysfunction in bipolar disorder]. 1622 Jun 55

Pituitary blastoma, a recently described tumor of the neonatal pituitary, exhibits differentiation to Rathke epithelium and adenohypophysial cells of folliculostellate and secretory type, a reflection of arrested pituitary development and unchecked proliferation (Scheithauer et al. in Acta Neuropathol 116(6):657-666, 2008). Herein, we report the pathologic features of three additional cases, all ACTH-producing. One involved a 9-month-old male presenting with progressive right ophthalmoplegia, MRI findings of a large suprasellar mass with cavernous sinus invasion, and elevated plasma ACTH levels. The second was nonfunctioning and occurred in a 13-month-old female with right third nerve palsy. The third had been previously published as a "pituitary adenoma" in a 2-year-old female (Min et al. in Pathol Int 57(9):600-605, 2007). The subtotally resected tumors were subject to histochemical, immunohistochemical and, in two cases, ultrastructural study. Histologically, the complex tumors consisted of glands of varying from rosettes to glandular structures resembling Rathke epithelium, small undifferentiated-appearing cells (blastema), and large secretory cells. Mucin-producing goblet cells were noted in case 3. Cell proliferation was high in two cases and low in case 3. Immunoreactivity of the secretory cells included synaptophysin, chromogranin, various keratins and, to a lesser extent, ACTH and beta endorphin. MGMT immunolabeling was 40-60%. Mitotic activity was moderate to high in cases 1 and 2 and was low in case 3. The same was true for MIB-1 labeling. Germ cell markers were lacking in all cases. One tumor ultrastructurally consisted of three cell populations including (a) small, polyhedral, primitive-appearing cells (blastema) with scant cytoplasm, abundant glycogen and few organelles, (b) folliculostellate cells and (c) large corticotroph cells containing rough endoplasmic reticulum, golgi membranes, spherical, 150-400 nm secretory granules and occasional perinuclear, intermediate filament bundles. A second example (case 3) lacked a blastema and glandular component. The clinical and morphologic features of our three cases were those of pituitary blastoma. The finding of cellular elements of adenohypophysial development is consistent with a diagnosis of pituitary blastoma and aligns it with blastomas of other organs. It also suggests an underlying specific genetic abnormality. Marked variations in cellular proliferative activity suggest blastomas occur in low- and higher-grade form. Variable MGMT reactivity suggests an incomplete response to temozolomide therapy. Literature regarding similar morphologically complex, infantile, Cushing disease-associated lesions is briefly reviewed.
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PMID:Pituitary blastoma: a unique embryonal tumor. 2180 93

A family with three affected males and a second family with a single affected male with intellectual disability, microcephaly, ophthalmoplegia, deafness, and Involuntary limb movements were reported by Schimke and Associates in 1984. The affected males with Schimke X-linked intellectual disability (XLID) syndrome (OMIM# 312840) had a similar facial appearance with deep-set eyes, downslanting palpebral fissures, hypotelorism, narrow nose and alae nasi, cupped ears and spacing of the teeth. Two mothers had mild hearing loss but no other manifestations of the disorder. The authors considered the disorder to be distinctive and likely X-linked. Whole genome sequencing in the single affected male available and the three carrier females from one of the families with Schimke XLID syndrome identified a 2 bp deletion in the BCAP31 gene. During the past decade, pathogenic alterations of the BCAP31 gene have been associated with deafness, dystonia, and central hypomyelination, an XLID condition given the eponym DDCH syndrome. A comparison of clinical findings in Schimke XLID syndrome and DDCH syndrome shows them to be the same clinical entity. The BCAP31 protein functions in endoplasmic reticulum-associated degradation to promote ubiquitination and destruction of misfolded proteins.
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PMID:Schimke XLID syndrome results from a deletion in BCAP31. 3268 19