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61.
Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy 总被引:2,自引:0,他引:2
Pan TC; Zhang RZ; Pericak-Vance MA; Tandan R; Fries T; Stajich JM; Viles K; Vance JM; Chu ML; Speer MC 《Human molecular genetics》1998,7(5):807-812
The Bethlem myopathy is a rare autosomal dominant proximal myopathy
characterized by early childhood onset and joint contractures. Evidence for
linkage and genetic heterogeneity has been established, with the majority
of families linked to 21q22.3 and one large family linked to 2q37,
implicating the three type VI collagen subunit genes, COL6A1 (chromosome
21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes.
Mutations of the invariant glycine residues in the triple-helical
domain-coding region of COL6A1 and COL6A2 have been reported previously in
the chromosome 21-linked families. We report here the identification of a
G-->A mutation in the N-terminal globular domain-coding region of COL6A3
in a large American pedigree (19 affected, 12 unaffected), leading to the
substitution of glycine by glutamic acid in the N2 motif, which is
homologous to the type A domains of the von Willebrand factor. This
mutation segregated to all affected family members, to no unaffected family
members, and was not identified in 338 unrelated Caucasian control
chromosomes. Thus mutations in either the triple-helical domain or the
globular domain of type VI collagen appear to cause Bethlem myopathy.
相似文献
62.
doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH) 总被引:12,自引:0,他引:12
des Portes V; Francis F; Pinard JM; Desguerre I; Moutard ML; Snoeck I; Meiners LC; Capron F; Cusmai R; Ricci S; Motte J; Echenne B; Ponsot G; Dulac O; Chelly J; Beldjord C 《Human molecular genetics》1998,7(7):1063-1070
Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical
dysgenesis disorder associated with a defect in neuronal migration.
Clinical manifestations are epilepsy and mental retardation. This disorder,
which mainly affects females, can be inherited in a single pedigree with
lissencephaly, a more severe disease which affects the male individuals.
This clinical entity has been described as X- SCLH/LIS syndrome. Recently
we have demonstrated that the doublecortin gene, which is localized on the
X chromosome, is implicated in this disorder. We have now performed a
systematic mutation analysis of doublecortin in 11 unrelated females with
SCLH (one familial and 10 sporadic cases) and have identified mutations in
10/11 cases. The sequence differences include nonsense, splice site and
missense mutations and these were found throughout the gene. These results
provide strong evidence that loss of function of doublecortin is the major
cause of SCLH. The absence of phenotype-genotype correlations suggests that
X-inactivation patterns of neuronal precursor cells are likely to
contribute to the variable clinical severity of this disorder in females.
相似文献
63.
64.
D Hassine G Rougereau JM Feron MC Henry-Feugeas V Fabre JC Sadik E Schouman-Claeys 《Surgical and radiologic anatomy : SRA》1994,16(3):293-301
Summary The angular points are the ligamentous and tendinous structures that reinforce the posteromedial and posterolateral capsule of the knee and share in fixation of the posterior horns of the menisci. They are often damaged in acute injuries and this is usually associated with ruptures of the cruciate and collateral ligaments and may add to the degree of laxity. We describe the normal appearance of these structures in terms of the sectional anatomy, correlated with the lesional appearances of complete and incomplete ruptures and associated meniscal detachments as shown by clinical testing and arthrotomy findings.
IRM des points d'angle du genou : bases anatomiques et applications aux genoux traumatiques
Résumé Les points d'angle sont des structures ligamentaires et tendineuses qui renforcent la capsule postéro-médiale et postéro-latérale et participent à la fixation des cornes postérieures des ménisques. Leurs lésions, fréquentes au cours des traumatismes aigus, sont généralement associées à des ruptures des ligaments croisés et des ligaments collatéraux et peuvent être source d'une aggravation de la laxité. Nous rapportons, en corrélation avec l'anatomie en coupe, l'aspect normal de ces structures, et en corrélation avec les données de l'arthrotomie et du testing les aspects lésionnels observés au cours des traumatismes : ruptures complètes, incomplètes et désinsertions méniscales associées.相似文献
65.
Inhibition of poly(ADP-ribose) polymerase attenuates the severity of acute pancreatitis and associated lung injury 总被引:4,自引:0,他引:4
Mota RA Sánchez-Bueno F Saenz L Hernández-Espinosa D Jimeno J Tornel PL Martínez-Torrano A Ramírez P Parrilla P Yélamos J 《Laboratory investigation; a journal of technical methods and pathology》2005,85(10):1250-1262
The severity of acute pancreatitis results from the transmigration and activation of leukocytes within the pancreas and the local synthesis and release of proinflammatory-soluble mediators that transform a local injury into a systemic inflammatory response. Poly(ADP-ribose)polymerase-1 (PARP-1) is a nuclear DNA-binding protein that has been shown to play a relevant role in cell necrosis and organ failure in various diseases associated with inflammation. Therefore, we set out to investigate whether the genetic deletion of PARP-1 or PARP-2 (a new member of the PARP family) genes, or pharmacological inhibition of PARP activity might affect the development and severity of acute pancreatitis and pancreatitis-associated lung injury. Secretagogue-induced acute pancreatitis was achieved by 12 hourly intraperitoneal injections of cerulein in mice deficient in PARP-1 or PARP-2 genes, and wild-type (WT) littermate mice untreated or treated with PARP activity inhibitors. The severity of pancreatitis was assessed by measurements of serum amylase, lipase, interleukin-1beta and IL-6, pancreatic water content, histologic grading and pancreas myeloperoxidase (MPO) activity. Lung injury was evaluated by quantifying MPO activity and morphological changes. We found that the severity of acute pancreatitis and pancreatitis-associated lung injury was significantly attenuated in mice lacking PARP-1, but not PARP-2, compared with WT mice. Interestingly, administration of PARP inhibitors, 3-aminobenzamide or PJ34 (N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethyacetamide HCl), in WT mice markedly decreased acute pancreatitis severity and pulmonary-associated injury in a larger extension than genetic deletion of PARP-1. Our results support the potential therapeutic application of PARP inhibitors in the development and severity of acute pancreatitis and associated lung injury. 相似文献
66.
Stein TP; Oram-Smith JC; Leskiw MJ; Wallace HW; Long LC; Leonard JM 《The American journal of physiology》1976,230(5):1321-1325
67.
68.
Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases 总被引:5,自引:2,他引:5
Huang JQ; Trasler JM; Igdoura S; Michaud J; Hanal N; Gravel RA 《Human molecular genetics》1997,6(11):1879-1885
Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative
diseases resulting from the inability to catabolize GM2 ganglioside by
beta-hexosaminidase A (Hex A) due to mutations of the alpha subunit
(Tay-Sachs disease) or beta subunit (Sandhoff disease) of Hex A. Hex B
(beta beta homodimer) is also defective in Sandhoff disease. We previously
developed mouse models of both diseases and showed that Hexa-/- (Tay-Sachs)
mice remain asymptomatic to at least 1 year of age while Hexb-/- (Sandhoff)
mice succumb to a profound neurodegenerative disease by 4-6 months of age.
Here we find that neuron death in Hexb-/- mice is associated with apoptosis
occurring throughout the CNS, while Hexa-/- mice were minimally involved at
the same age. Studies of autopsy samples of brain and spinal cord from
human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances,
in keeping with the severe expression of both diseases. We suggest that
neuron death is caused by unscheduled apoptosis, implicating accumulated
GM2 ganglioside or a derivative in triggering of the apoptotic cascade.
相似文献
69.
The bias favoring deletion over inversion in DH-JH rearrangement has been
known for years, but the underlying mechanism has yet to be fully defined.
It has been suggested that the ratio of deletion/inversion is determined by
the combined effect of two factors: (i) the relative strengths of 5' and 3'
recombination signal sequences (RSS) of a DH segment, and (ii) the
efficiency with which the deletional product (one joint) forms relative to
the inversional product (two joints). In this study, we analyzed for the
first time the effect of factor 1 alone on the biased 3' RSS utilization in
DH-JH joining by using deletional plasmids in an extrachromosomal substrate
V(D)J recombination assay. It was found that the 3' RSS and associated
coding end (12 bp) mediate recombination more efficiently than the 5'
RSS/coding end DH-JH plasmids. These results demonstrate that the effect of
the RSS/coding end alone can account, at least partially, for the
predominant deletion in DH-JH recombination. The potential effect of the
relative strength of RSS and associated coding end on the ordered
rearrangement of DH-JH followed by VH to DH-JH was also assessed. When
recombination frequencies of D-->J (3' DH to J3) were compared with
frequencies of V-- >D (VHPJ14 to 3' DH or VHOX2 to 3' DH), it was found
that V-->D joining was, if anything, more efficient than D-->J
joining. Therefore, if all three segments were accessible, RSS/coding end
effects would not contribute to the ordered rearrangement of the IgH locus.
相似文献
70.
JM Hopkin 《Current opinion in immunology》1997,9(6):788-792
Atopy — a T helper 2 cell driven hypersensitivity to innocuous antigens (allergens) which causes most cases of asthma — is of complex genetic and environmental origins. There is compelling epidemiological evidence for a rise in atopic disease in ‘westernised’ communities. The changing pattern of microbial exposure in early childhood is suggested to be the principal candidate mechanism for this rise. 相似文献