Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
 
Articles by M. Koenig
Total Records ( 2 ) for M. Koenig
  M Anheim , B Monga , M Fleury , P Charles , C Barbot , M Salih , J. P Delaunoy , M Fritsch , L Arning , M Synofzik , L Schols , J Sequeiros , C Goizet , C Marelli , I Le Ber , J Koht , J Gazulla , J De Bleecker , M Mukhtar , N Drouot , L Ali Pacha , T Benhassine , M Chbicheb , A M'Zahem , A Hamri , B Chabrol , J Pouget , R Murphy , M Watanabe , P Coutinho , M Tazir , A Durr , A Brice , C Tranchant and M. Koenig
 

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found. In patients with AOA2, median AFP serum level was 31.0 µg/l at diagnosis, which was higher than the median AFP level of AOA2 negative patients: 13.8 µg/l, P = 0.0004; itself higher than the normal level (3.4 µg/l, range from 0.5 to 17.2 µg/l) because elevated AFP was one of the possible selection criteria. Polyneuropathy was found in 97.5% of AOA2 patients, cerebellar atrophy in 96%, occasional oculomotor apraxia in 51%, pyramidal signs in 20.5%, head tremor in 14%, dystonia in 13.5%, strabismus in 12.3% and chorea in 9.5%. No patient was lacking both peripheral neuropathy and cerebellar atrophy. The age at onset and presence of occasional oculomotor apraxia were negatively correlated to the progression rate of the disease (P = 0.03 and P = 0.009, respectively), whereas strabismus was positively correlated to the progression rate (P = 0.03). An increased AFP level as well as cerebellar atrophy seem to be stable in the course of the disease and to occur mostly at or before the onset of the disease. One of the two patients with a normal AFP level at diagnosis had high AFP levels 4 years later, while the other had borderline levels. The probability of missing AOA2 diagnosis, in case of sequencing senataxin gene only in non-Friedreich ataxia non-ataxia-telangiectasia ataxic patients with AFP level ≥7 µg/l, is 0.23% and the probability for a non-Friedreich ataxia non-ataxia-telangiectasia ataxic patient to be affected with AOA2 with AFP levels ≥7 µg/l is 46%. Therefore, selection of patients with an AFP level above 7 µg/l for senataxin gene sequencing is a good strategy for AOA2 diagnosis. Pyramidal signs and dystonia were more frequent and disease was less severe with missense mutations in the helicase domain of senataxin gene than with missense mutations out of helicase domain and deletion and nonsense mutations (P = 0.001, P = 0.008 and P = 0.01, respectively). The lack of pyramidal signs in most patients may be explained by masking due to severe motor neuropathy.

  M Assoum , M. A Salih , N Drouot , D H'Mida Ben Brahim , C Lagier Tourenne , A AlDrees , S. A Elmalik , T. S Ahmed , M. Z Seidahmed , M. M Kabiraj and M. Koenig
 

We have identified a novel form of recessive ataxia that segregates in three children of a large consanguineous Saudi Arabian family. The three patients presented with childhood onset gait and limb ataxia, dysarthria and had limited walking without aid into their teenage years. Two patients developed epilepsy at 7 months without relapse after treatment, and mental retardation. Linkage studies allowed us to identify a single locus that segregated with the disease on chromosome 3q28-qter. Mutation screening of all coding sequences revealed a single nucleotide deletion, 2927delC, in exon 19 of the KIAA0226 gene, which results in a frame shift of the C-terminal domain (p.Ala943ValfsX146). The KIAA0226 gene encodes a protein that we named rundataxin, with two conserved domains: an N-terminal RUN domain and a C-terminal domain containing a diacylglycerol binding-like motif. The closest paralogue of rundataxin, the plekstrin homology domain family member M1, has been shown to colocalize with Rab7, a small GTPase associated with late endosomes/lysosomes, suggesting that rundataxin may also be associated with vesicular trafficking and signalling pathways through its RUN and diacylglycerol binding-like domains. The rundataxin pathway appears therefore distinct from the ataxia pathways involving deficiency in mitochondrial or nuclear proteins and broadens the range of mechanisms leading to recessive ataxias.

 
 
 
Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility