Stucka R

References (3)

Title : Synaptic congenital myasthenic syndrome in three patients due to a novel missense mutation (T441A) of the COLQ gene - Muller_2004_Neuropediatrics_35_183
Author(s) : Muller JS , Petrova S , Kiefer R , Stucka R , Konig C , Baumeister SK , Huebner A , Lochmuller H , Abicht A
Ref : Neuropediatrics , 35 :183 , 2004
Abstract : Congenital myasthenic syndromes (CMS) with deficiency of endplate acetylcholinesterase (AChE) are caused by mutations in the synapse specific collagenic tail subunit gene (COLQ) of AChE. We identified a novel missense mutation (T441A) homozygously in three CMS patients from two unrelated German families. The mutation is located in the C-terminal region of the ColQ protein, which initiates assembly of the triple helix, and is essential for insertion of the tail subunit into the basal lamina. Density gradient analysis of AChE extracted from muscle of one of the patients revealed the absence of asymmetric AChE. All patients were characterized by an onset of disease in childhood, exercise-induced proximal weakness, absence of ptosis and ophthalmoparesis, a decremental EMG response, and deterioration in response to anticholinesterase drugs. However, age at onset, disease progression, disease severity, and functional impairment varied considerably among the three patients. As adults, two siblings from one family experience only mild impairment, while the third patient requires a wheelchair for most of the day and assisted ventilation at night.
ESTHER : Muller_2004_Neuropediatrics_35_183
PubMedSearch : Muller_2004_Neuropediatrics_35_183
PubMedID: 15248101

Title : A newly identified chromosomal microdeletion and an N-box mutation of the AChR epsilon gene cause a congenital myasthenic syndrome - Abicht_2002_Brain_125_1005
Author(s) : Abicht A , Stucka R , Schmidt C , Briguet A , Hopfner S , Song IH , Pongratz D , Muller-Felber W , Ruegg MA , Lochmuller H
Ref : Brain , 125 :1005 , 2002
Abstract : Congenital myasthenic syndromes (CMSs) are frequently caused by mutations of the coding region of the acetylcholine receptor epsilon subunit (AChRepsilon) gene leading to a reduced expression of the acetylcholine receptor (AChR) at the postsynaptic membrane. Two recent observations have linked two different N-box mutations of the human AChRepsilon promoter to a clinical CMS phenotype. N-boxes are regulatory sequence elements of mammalian promoters that confer synapse-specific expression of several genes, including the AChR subunit genes. Here, we report on a novel point mutation (epsilon-154G-->A) in the N-box of the AChRepsilon promoter in a German CMS pedigree. Semiquantitative analysis of AChRepsilon mRNA levels in the patient's muscle indicated significantly impaired AChRepsilon expression. We provide additional evidence of a pathogenic role for this mutation using the mutated promoter (epsilon-154G-->A) driving a heterologous gene (luciferase) in rat skeletal muscle. We show that agrin-induced gene expression is significantly reduced by the N-box mutant (mt) compared with the wild-type (wt) promoter. Refined haplotype analysis and direct sequencing revealed maternal inheritance of the mutant AChRepsilon promoter (epsilon-154G-->A) together with paternal inheritance of a chromosomal microdeletion (Delta1290 bp) encompassing the promoter and the first two exons of the AChRepsilon gene in the index patient. In conclusion, we provide genetic and functional evidence that a mutation of the AChRepsilon subunit promoter (epsilon-154G-->A) causes CMS due to the reduction of gene expression in skeletal muscle. Moreover, this is the first report of a chromosomal microdeletion affecting an AChR gene. This type of mutation may be missed in standard screening techniques of CMS patients.
ESTHER : Abicht_2002_Brain_125_1005
PubMedSearch : Abicht_2002_Brain_125_1005
PubMedID: 11960891

Title : Complete DNA sequence of yeast chromosome II - Feldmann_1994_EMBO.J_13_5795
Author(s) : Feldmann H , Aigle M , Aljinovic G , Andre B , Baclet MC , Barthe C , Baur A , Becam AM , Biteau N , Boles E , Brandt T , Brendel M , Bruckner M , Bussereau F , Christiansen C , Contreras R , Crouzet M , Cziepluch C , Demolis N , Delaveau T , Doignon F , Domdey H , Dusterhus S , Dubois E , Dujon B , El Bakkoury M , Entian KD , Feurmann M , Fiers W , Fobo GM , Fritz C , Gassenhuber H , Glandsdorff N , Goffeau A , Grivell LA , de Haan M , Hein C , Herbert CJ , Hollenberg CP , Holmstrom K , Jacq C , Jacquet M , Jauniaux JC , Jonniaux JL , Kallesoe T , Kiesau P , Kirchrath L , Kotter P , Korol S , Liebl S , Logghe M , Lohan AJ , Louis EJ , Li ZY , Maat MJ , Mallet L , Mannhaupt G , Messenguy F , Miosga T , Molemans F , Muller S , Nasr F , Obermaier B , Perea J , Pierard A , Piravandi E , Pohl FM , Pohl TM , Potier S , Proft M , Purnelle B , Ramezani Rad M , Rieger M , Rose M , Schaaff-Gerstenschlager I , Scherens B , Schwarzlose C , Skala J , Slonimski PP , Smits PH , Souciet JL , Steensma HY , Stucka R , Urrestarazu A , van der Aart QJ , van Dyck L , Vassarotti A , Vetter I , Vierendeels F , Vissers S , Wagner G , de Wergifosse P , Wolfe KH , Zagulski M , Zimmermann FK , Mewes HW , Kleine K , Dsterhus S , Mller S , Pirard A , Schaaff-Gerstenschlger I
Ref : EMBO Journal , 13 :5795 , 1994
Abstract : In the framework of the EU genome-sequencing programmes, the complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome II (807 188 bp) has been determined. At present, this is the largest eukaryotic chromosome entirely sequenced. A total of 410 open reading frames (ORFs) were identified, covering 72% of the sequence. Similarity searches revealed that 124 ORFs (30%) correspond to genes of known function, 51 ORFs (12.5%) appear to be homologues of genes whose functions are known, 52 others (12.5%) have homologues the functions of which are not well defined and another 33 of the novel putative genes (8%) exhibit a degree of similarity which is insufficient to confidently assign function. Of the genes on chromosome II, 37-45% are thus of unpredicted function. Among the novel putative genes, we found several that are related to genes that perform differentiated functions in multicellular organisms of are involved in malignancy. In addition to a compact arrangement of potential protein coding sequences, the analysis of this chromosome confirmed general chromosome patterns but also revealed particular novel features of chromosomal organization. Alternating regional variations in average base composition correlate with variations in local gene density along chromosome II, as observed in chromosomes XI and III. We propose that functional ARS elements are preferably located in the AT-rich regions that have a spacing of approximately 110 kb. Similarly, the 13 tRNA genes and the three Ty elements of chromosome II are found in AT-rich regions. In chromosome II, the distribution of coding sequences between the two strands is biased, with a ratio of 1.3:1. An interesting aspect regarding the evolution of the eukaryotic genome is the finding that chromosome II has a high degree of internal genetic redundancy, amounting to 16% of the coding capacity.
ESTHER : Feldmann_1994_EMBO.J_13_5795
PubMedSearch : Feldmann_1994_EMBO.J_13_5795
PubMedID: 7813418
Gene_locus related to this paper: yeast-LDH1 , yeast-MCFS2 , yeast-yby9