Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038379 (strabismus)
 9,317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied by light and electron microscopy the diffuse iris nevus of an eye in a 16-year-old patient with oculodermal melanocytosis and choroidal malignant melanoma. The nevus cells in the anterior border layer of the iris appeared to be poorly differentiated, showing moderate infolding of the nuclear membrane with heterochromatin clumping, watery cytoplasm, abundant mitochondria, fine filaments, rough endoplasmic reticulum, and numerous pinocytotic vesicles. Small scattered immature melanosomes and occasional giant melanosomes were observed in these cells. Deep in the iris stroma, however, nevus cells were found singly or in small groups, and were associated with an increasing number of melanized melanosomes and cytoplasmic filaments and reduced numbers of other cytoplasmic organelles, such as mitochondria and free ribosomes. Differentiation of the iris nevus cells appeared to progress from the anterior border layer toward the iris stroma. This observation suggests that intrastromal nevi may be more benign than nevi with surface plaque. The ultrastructural characteristics of the diffuse nevi of oculodermal melanocytosis were compared with those of other iris nevi.
J Pediatr Ophthalmol Strabismus
PMID:Diffuse iris nevus in oculodermal melanocytosis: a light and electron microscopic study. 279 14

During early vertebrate development, a signaling network is activated along the midline of the embryo. This signaling network induces the neural tube floor plate and ventral brain regions. In turn, induction of the ventral brain region is important for bilateral division of the forebrain and bilateral separation of the eyes. The present study provides direct evidence for a role of the endoplasmic reticulum Ca(2+) pump in zebrafish midline signaling. The endoplasmic reticulum Ca(2+) pump was inhibited in zebrafish embryos using thapsigargin or cyclopiazonic acid. Inhibition of the endoplasmic reticulum Ca(2+) pump during early gastrulation induces cyclopia, mimicking defects observed in cyclops, squint, one-eyed pinhead, and silberblick mutant embryos. In contrast, inhibition of the endoplasmic reticulum Ca(2+) pump during mid-gastrulation does not induce cyclopia, but does induce tail defects, mimicking defects observed in no-tail mutant embryos. This study is the first to relate thapsigargin and cyclopiazonic acid with induction of cyclopia. In addition, obtained results provide new information on the roles of Ca(2+) in embryonic development and may lead to new insights on the mechanisms underlying holoprosencephaly, a relatively common brain defect in human development.
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PMID:The calcium pump of the endoplasmic reticulum plays a role in midline signaling during early zebrafish development. 1524 90

Mucolipidosis type IV is an autosomal recessive lysosomal storage disorder characterized by severe neurodegeneration, achlorhydria, and visual impairments such as corneal opacity and strabismus. The disease arises due to mutations in a group 2 transient receptor potential (TRP)-related cation channel, TRPML1. Mammals encode two additional TRPML proteins named TRPML2 and TRPML3. Information regarding the propensity of these proteins to multimerize, their subcellular distribution and mechanisms that regulate their trafficking are limited. Here we demonstrate that TRPMLs interact to form homo- and heteromultimers. Moreover, the presence of either TRPML1 or TRPML2 specifically influences the spatial distribution of TRPML3. TRPML1 and TRPML2 homomultimers are lysosomal proteins, whereas TRPML3 homomultimers are in the endoplasmic reticulum. However, TRPML3 localizes to lysosomes when coexpressed with either TRPML1 or TRPML2 and is comparably mislocalized when lysosomal targeting of TRPML1 and TRPML2 is disrupted. Conversely, TRPML3 does not cause retention of TRPML1 or TRPML2 in the endoplasmic reticulum. These data demonstrate that there is a hierarchy controlling the subcellular distributions of the TRPMLs such that TRPML1 and TRPML2 dictate the localization of TRPML3 and not vice versa.
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PMID:Lysosomal localization of TRPML3 depends on TRPML2 and the mucolipidosis-associated protein TRPML1. 1660 12

SQN (SQUINT) is the Arabidopsis ortholog of the immunophilin CyP40 (cyclophilin 40) and promotes microRNA activity by promoting the activity of AGO1. In animals and Saccharomyces cerevisiae, CyP40 promotes protein activity in association with the protein chaperone Hsp90. To determine whether CyP40 also acts in association with Hsp90 in plants, we examined the interaction between SQN and Hsp90 in vitro and tested the importance of this interaction for the function of SQN in planta. We found that SQN interacts with cytoplasmic Hsp90 proteins but not with Hsp90 proteins localized to chloroplasts, mitochondria, or the endoplasmic reticulum. The interaction between SQN and Hsp90 in vitro requires the MEEVD domain of Hsp90, as well as several conserved amino acids within the tetratricopeptide repeat domain of SQN. Amino acid substitutions that disrupt the interaction between SQN and Hsp90 in vitro also impair the activity of SQN in planta. Our results indicate that the interaction between CyP40 and Hsp90 is conserved in plants and that this interaction is essential for the function of CyP40.
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PMID:Binding of the cyclophilin 40 ortholog SQUINT to Hsp90 protein is required for SQUINT function in Arabidopsis. 2190 11

NGLY1-related disorder is a newly described autosomal recessive condition characterized by neurological, hepatic, ophthalmological findings and associated with dysmorphic features, constipation and scoliosis. It is caused by mutations in NGLY1, which encodes an enzyme, N-glycanase 1, involved in deglycosylation of glycoproteins, an essential step in the endoplasmic reticulum-associated degradation (ERAD) pathway. The disorder has been described in eight patients. We investigated the molecular basis and phenotype of NGLY1-related disorder in an additional patient. The proband is a 14-year-old who presented in early infancy with profound hypotonia and elevated transaminases. Liver biopsy showed lipid accumulation with dilated endoplasmic reticulum. He exhibited global developmental delay, acquired microcephaly, seizures, involuntary body movements, muscle atrophy, absent reflexes, and poor growth. He had multiple procedures for lacrimal duct stenosis and strabismus and had intractable blepharitis. He had severe osteopenia and persistent hypocholesterolemia. Whole exome sequencing revealed two novel variants in NGLY1: a truncating mutation, c.347C > G (p.S116X), and a splicing mutation, c.881 + 5G (p.IVS5 + 5G>T), predicted to abolish the splice donor site of exon 5. This study, along with previously reported cases, suggests that mutations in NGLY1 cause a recognizable phenotype and targeted sequencing should be considered in patients with typical presentation. This study expands the molecular spectrum of NGLY1-related condition and suggests that osteopenia and hypocholesterolemia may be part of the phenotype.
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PMID:Multi-systemic involvement in NGLY1-related disorder caused by two novel mutations. 2570 56