University of Graz

About: University of Graz is a education organization based out in Graz, Steiermark, Austria. It is known for research contribution in the topics: Population & Quantum chromodynamics. The organization has 17934 authors who have published 37489 publications receiving 1110980 citations. The organization is also known as: Carolo Franciscea Graecensis & Karl Franzens Universität.

Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome

Abstract: Distal hereditary motor neuropathy (dHMN) or distal spinal muscular atrophy (OMIM #182960) is a heterogeneous group of disorders characterized by an almost exclusive degeneration of motor nerve fibers, predominantly in the distal part of the limbs(1). Silver syndrome (OMIM #270685) is a rare form of hereditary spastic paraparesis mapped to chromosome 11q12q14 (SPG17) in which spasticity of the legs is accompanied by amyotrophy of the hands and occasionally also the lower limbs(2,3). Silver syndrome and most forms of dHMN are autosomal dominantly inherited with incomplete penetrance and a broad variability in clinical expression. A genome-wide scan in an Austrian family with dHMN-V (ref. 4) showed linkage to the locus SPG17, which was confirmed in 16 additional families with a phenotype characteristic of dHMN or Silver syndrome. After refining the critical region to 1 Mb, we sequenced the gene Berardinelli-Seip congenital lipodystrophy (BSCL2) and identified two heterozygous missense mutations resulting in the amino acid substitutions N88S and S90L. Null mutations in BSCL2, which encodes the protein seipin, were previously shown to be associated with autosomal recessive Berardinelli-Seip congenital lipodystrophy 5 (OMIM #269700). We show that seipin is an integral membrane protein of the endoplasmic reticulum (ER). The amino acid substitutions N88S and S90L affect glycosylation of seipin and result in aggregate formation leading to neurodegeneration.

Criteria for an increased specificity of MRI interpretation in elderly subjects with suspected multiple sclerosis

Abstract: We reviewed the MRIs of 49 asymptomatic volunteers (age range, 31 to 77 years) and of 50 MS patients (age range, 14 to 63) for areas of increased signal (AIS) and features discriminating MS lesions from lesions seen with normal aging. We obtained optimal specificity of MRI interpretation (100%) if we required at least two of the following three AIS features--size greater than or equal to 6 mm, abutting ventricular bodies, infratentorial location--for a positive MRI diagnosis of MS. Applying these criteria to the MRIs of elderly patients with suspected MS should significantly improve specificity (p less than 0.001) over current quantitative criteria (at least three AIS greater than or equal to 3 mm) without significantly decreasing sensitivity.