Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report three patients with slowly progressive spastic paraplegia and dementia; MRI on these patients revealed hypoplasia of the corpus callosum. The mode of inheritance was supposed to be autosomal recessive. Patient 1 (26-year-old man) is an elder brother of patient 2 (21-year-old man). Their parents are first cousins. Patient 3 (woman), a sporadic case, died of pneumonia at the age of 44. Their motor development after the birth was normal, but patient 3 was mildly mentally retarded. Gait disturbance due to spastic paraplegia developed at the age of nine (patient 2), fifteen (patient 1) and nineteen (patient 3), respectively. They also showed slowly progressive mental deterioration. Patient 1 has also suffered from mild amyotrophy and sensory disturbance in the distal part of the extremities since the age of 25. Patient 3 was bed-ridden at the middle of her thirty's because of generalized amyotrophy and sensory disturbance in addition to spastic quadriplegia and profound dementia. Their MRI reveal the thinning of the corpus callosum. We think the thinning must be hypoplasia of the corpus callosum, because the cerebrum showed normal appearance on MRI in patient 1 and patient 2. These clinical findings and imaging studies are essentially similar to those of the cases reported by Iwabuchi et al (1991). We propose autosomal recessive HSP associated hypoplasia of the corpus callosum as a new type of HSP.
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PMID:[Three patients of complicated form of autosomal recessive hereditary spastic paraplegia associated with hypoplasia of the corpus callosum]. 782 9

Our objective was to estimate the frequency as well as to establish the clinical and neuroimaging profile of hereditary spastic paraplegia with thin corpus callosum (HSP-TCC). HSP-TCC was recognized as a specific clinical subtype of HSP and mapped to chromosome (ch) 15q13-15 in Japanese families. It has been considered rare in western countries. We assessed 45 patients with autosomal recessive HSP from 20 different families in search of clinical and imaging criteria for the diagnosis of HSP-TCC. In addition, HSP-TCC patients underwent further neurological, imaging and genetic evaluation. MRI scans were performed in a 2T scanner and sagittal T1 weighted images used for semiautomated volumetric measurements of corpus callosum, cerebellum, and brain. In seven patients, a 2-year follow-up MRI scan was performed. We genotyped seven microsatellite markers flanking the 15q13-15 candidate region and calculated two-point and multipoint LOD scores (Z). We identified 13 patients from seven unrelated families with HSP-TCC. MRI showed significant corpus callosum, cerebral and cerebellar volumetric reductions (P<0.001, P=0.03, and P=0.01, respectively). In the prospective analysis, we found progressive corpus callosum atrophy (P=0.04). Two-point and multipoint LOD scores were significantly negative for markers genotyped on ch 15q. However, independent pedigree analysis did not yield significant results. HSP-TCC was found in 35% of families with autosomal recessive HSP. MRI volumetry showed cerebral and cerebellar atrophy in association with progressive corpus callosum thinning. Genetic studies did not show evidence for linkage to ch 15q.
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PMID:Prospective neuroimaging study in hereditary spastic paraplegia with thin corpus callosum. 1751 53

Three-dimensional magnetic resonance imaging of the brain was analyzed using optimized voxel-based morphometry in 21 patients with pure hereditary spastic paraparesis (pHSP) and 12 patients with complicated HSP (cHSP). PHSP patients showed only small regional grey matter volume reduction, whereas significantly decreased grey matter volumes were localized pericentrally in cHSP. In the white matter, several small areas of regional volume reduction were observed in the pHSP patients, whereas the cHSP group exhibited large robust volume reduction involving the entire corpus callosum, a result that was reproduced by an additional region-based MRI analysis. It could be demonstrated that the topography of cerebral volume changes differed markedly in pHSP or cHSP at group level. Corpus callosum thinning seems to be a general feature of cHSP.
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PMID:Different regional brain volume loss in pure and complicated hereditary spastic paraparesis: a voxel-based morphometric study. 1785 8

Shortened telomeres are a normal consequence of cell division. However, telomere shortening past a critical point results in cellular senescence and death. To determine the effect of telomere shortening on lung, four generations of B6.Cg-Terc(tm1Rdp) mice, null for the terc component of telomerase, the holoenzyme that maintains telomeres, were bred and analyzed. Generational inbreeding of terc-/- mice caused sequential shortening of telomeres. Lung histology from the generation with the shortest telomeres (terc-/- F4) showed alveolar wall thinning and increased alveolar size. Morphometric analysis confirmed a significant increase in mean linear intercept (MLI). terc-/- F4 lung showed normal elastin deposition but had significantly decreased collagen content. Both airway and alveolar epithelial type 1 cells (AEC1) appeared normal by immunohistochemistry, and the percentage of alveolar epithelial type 2 cells (AEC2) per total cell number was similar to wild type. However, because of a decrease in distal lung cellularity, the absolute number of AEC2 in terc-/- F4 lung was significantly reduced. In contrast to wild type, terc-/- F4 distal lung epithelium from normoxia-maintained mice exhibited DNA damage by terminal deoxynucleotidyltransferase (TdT)-mediated dUTP nick end labeling (TUNEL) and 8-oxoguanine immunohistochemistry. Western blotting of freshly isolated AEC2 lysates for stress signaling kinases confirmed that the stress-activated protein kinase (SAPK)/c-Jun NH(2)-terminal kinase (JNK) stress response pathway is stimulated in telomerase-null AEC2 even under normoxic conditions. Expression of downstream apoptotic/stress markers, including caspase-3, caspase-6, Bax, and HSP-25, was also observed in telomerase-null, but not wild-type, AEC2. TUNEL analysis of freshly isolated normoxic AEC2 showed that DNA strand breaks, essentially absent in wild-type cells, increased with each successive terc-/- generation and correlated strongly with telomere length (R(2) = 0.9631). Thus lung alveolar integrity, particularly in the distal epithelial compartment, depends on proper telomere maintenance.
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PMID:Lung alveolar integrity is compromised by telomere shortening in telomerase-null mice. 1895 56

Autosomal recessive spastic paraplegia with thinning of corpus callosum (ARHSP-TCC) is a complex form of HSP initially described in Japan but subsequently reported to have a worldwide distribution with a particular high frequency in multiple families from the Mediterranean basin. We recently showed that ARHSP-TCC is commonly associated with mutations in SPG11/KIAA1840 on chromosome 15q. We have now screened a collection of new patients mainly originating from Italy and Brazil, in order to further ascertain the spectrum of mutations in SPG11, enlarge the ethnic origin of SPG11 patients, determine the relative frequency at the level of single Countries (i.e., Italy), and establish whether there is one or more common mutation. In 25 index cases we identified 32 mutations; 22 are novel, including 9 nonsense, 3 small deletions, 4 insertions, 1 in/del, 1 small duplication, 1 missense, 2 splice-site, and for the first time a large genomic rearrangement. This brings the total number of SPG11 mutated patients in the SPATAX collection to 111 cases in 44 families and in 17 isolated cases, from 16 Countries, all assessed using homogeneous clinical criteria. While expanding the spectrum of mutations in SPG11, this larger series also corroborated the notion that even within apparently homogeneous population a molecular diagnosis cannot be achieved without full gene sequencing.
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PMID:Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion. 1910 90