Mutations in the Fatty Acid 2-Hydroxylase Gene Are Associated with Leukodystrophy with Spastic Paraparesis and Dystonia

Myelination is a complex, developmentally regulated process whereby myelin proteins and lipids are coordinately expressed by myelinating glial cells. Homozygosity mapping in nine patients with childhood onset spasticity, dystonia, cognitive dysfunction, and periventricular white matter disease revealed inactivating mutations in the FA2H gene. FA2H encodes the enzyme fatty acid 2-hydroxylase that catalyzes the 2-hydroxylation of myelin galactolipids, galactosylceramide, and its sulfated form, sulfatide. To our knowledge, this is the first identified deficiency of a lipid component of myelin and the clinical phenotype underscores the importance of the 2-hydroxylation of galactolipids for myelin maturation. In patients with autosomal-recessive unclassified leukodystrophy or complex spastic paraparesis, sequence analysis of the FA2H gene is warranted

Atlas Guided Identification . . .

This study presents a novel automatic approach for the identification of anatomical brain structures in magnetic resonance images (MRI). The method combines a fast multiscale multi-channel three dimensional (3D) segmentation algorithm providing a rich feature vocabulary together with a support vector machine (SVM) based classifier. The segmentation produces a full hierarchy of segments, expressed by an irregular pyramid with only linear time complexity. The pyramid provides a rich, adaptive representation of the image, enabling detection of various anatomical structures at different scales. A key aspect of the approach is the thorough set of multiscale measures employed throughout the segmentation process which are also provided at its end for clinical analysis. These features include in particular the prior probability knowledge of anatomic structures due to the use of an MRI probabilistic atlas. An SVM classifier is trained based on this set of features to identify the brain structures. We validated the approach using a gold standard real brain MRI data set. Comparison of the results with existing algorithms displays the promise of our approach

Deleterious Mutation in the Mitochondrial Arginyl–Transfer RNA Synthetase Gene Is Associated with Pontocerebellar Hypoplasia

Homozygosity mapping was performed in a consanguineous Sephardic Jewish family with three patients who presented with severe infantile encephalopathy associated with pontocerebellar hypoplasia and multiple mitochondrial respiratory-chain defects. This resulted in the identification of an intronic mutation in RARS2, the gene encoding mitochondrial arginine–transfer RNA (tRNA) synthetase. The mutation was associated with the production of an abnormally short RARS2 transcript and a marked reduction of the mitochondrial tRNAArg transcript in the patients’ fibroblasts. We speculate that missplicing mutations in mitochondrial aminoacyl-tRNA synthethase genes preferentially affect the brain because of a tissue-specific vulnerability of the splicing machinery

Joubert Syndrome 2 (JBTS2) in Ashkenazi Jews Is Associated with a TMEM216 Mutation

Patients with Joubert syndrome 2 (JBTS2) suffer from a neurological disease manifested by psychomotor retardation, hypotonia, ataxia, nystagmus, and oculomotor apraxia and variably associated with dysmorphism, as well as retinal and renal involvement. Brain MRI results show cerebellar vermis hypoplasia and additional anomalies of the fourth ventricle, corpus callosum, and occipital cortex. The disease has previously been mapped to the centromeric region of chromosome 11. Using homozygosity mapping in 13 patients from eight Ashkenazi Jewish families, we identified a homozygous mutation, R12L, in the TMEM216 gene, in all affected individuals. Thirty individuals heterozygous for the mutation were detected among 2766 anonymous Ashkenazi Jews, indicating a carrier rate of 1:92. Given the small size of the TMEM216 gene relative to other JBTS genes, its sequence analysis is warranted in all JBTS patients, especially those who suffer from associated anomalies. © 2010 The American Society of Human Genetics

Automatic Three-Dimensional Segmentation of MR Images Applied to the Rat Uterus

We introduce an automatic 3D multiscale automatic segmentation algorithm for delineating specific organs in Magnetic Resonance images (MRI). The algorithm can process several modalities simultaneously, and handle both isotropic and anisotropic data in only linear time complexity. It produces a hierarchical decomposition of MRI scans. During this segmentation process a rich set of features describing the segments in terms of intensity, shape and location are calculated, reflecting the formation of the hierarchical decomposition. We show that this method can delineate the entire uterus of the rat abdomen in 3D MR images utilizing a combination of scanning protocols that jointly achieve high contrast between the uterus and other abdominal organs and between inner structures of the rat uterus. Both single and multi-channel automatic segmentation demonstrate high correlation to a manual segmentation. While the focus here is on the rat uterus, the general approach can be applied to recognition in 2D, 3D and multi-channel medical images