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This Month in Archives of Neurology
March 2008

This Month in Archives of Neurology

Arch Neurol. 2008;65(3):301-302. doi:10.1001/archneur.65.3.301

Neuromics 2008 part i

Stem Cells on the Brain

The fact that 2 genes required for brain growth are also essential for normal chromatin structure suggests that the global chromatin activity state of neural stem cells is a key factor in regulation of brain mass. KnoepflerArticle, in this review, focuses on the links between neural stem cell chromatin and brain growth.

The HapMap

Hardy and SingletonArticle point out that the systematic identification of polymorphisms across the human genome has led to the discovery that, in any population, gene variability is not random and that variability at one position can predict with reasonable accuracy adjacent variability. This realization has been systematized into a knowledge base of the human HapMap, which has cataloged those single-nucleotide polymorphisms that can be used to capture the majority of human variability and to measure risk for complex neurological diseases.

Retromer Sorting and Alzheimer Disease

SmallArticle describes the studies that show that retromer sorting traffics proteins along the endosome-transgolgi network pathway and that retromer defects are implicated in late-onset Alzheimer disease. He reviews the details of the retromer sorting pathway and presents a cell biological model that can account for disease pathogenesis.

Neuromics and Alzheimer Disease

Waring and RosenbergArticle emphasize that genome-wide association studies have emerged as an increasingly effective tool for identifying contributions to complex diseases and represent the next frontier for furthering our understanding of the underlying etiologic, biologic, and pathologic mechanisms associated with chronic complex disorders such as Alzheimer disease.

Pharmaconeuromics of Interferon Beta in Multiple Sclerosis

Byun and colleaguesArticle use a genome-wide pharmacogenomic approach to identify single-nucleotide polymorphism allelic differences associated with interferon beta response in a cohort of 206 patients with relapsing-remitting multiple sclerosis followed up prospectively for 2 years after initiation of treatment. They report that many of the detected single-nucleotide polymorphism differences between drug responders and nonresponders were genes associated with ion channels and signal transduction pathways. The study also suggests that genetic variants in heparin sulfate proteoglycan genes may be of clinical interest in multiple sclerosis as predictors of the response to therapy. Here is an important advance in which a neuromic analysis has led to a pharmoconeuromic result having a direct therapeutic implication.

Maternal Transmission of Multiple Sclerosis

Hoppenbrouwers et alArticle find that there is a higher prevalence of maternal transmission of multiple sclerosis in a Dutch population. The kinship between mothers of patients was 3.8 times higher than between fathers. The most likely explanation is a gene-environment effect that takes place in utero.

Interferon Gamma Polymorphisms and Multiple Sclerosis

Kantarci and colleaguesArticle report that interferon gamma polymorphisms are associated with susceptibility to multiple sclerosis in men but not in women. The sex-specific susceptibility markers, of which rs2069727 was the strongest, were confined to interferon gamma.

Cortical Brain Malformations: A New Look

de Wit et alArticle evaluate the etiology of malformations of cortical development (MCD) in children and the impact of a combined radiological, clinical, and syndrome classification. Using this combined approach, a specific diagnosis was provided in 40% of the MCD cases. This, they indicate, will aid in the diagnosis prenatally and lead to improvement of patient and disease management.

MELAS or Leigh Syndrome Due to a Mutation in Mitochondrial DNA

Shanske and colleaguesArticle find that the G13513A mutation in the ND5 gene is a common cause of MELAS (a syndrome consisting of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) (3 patients) or Leigh syndrome (9 patients), even in the absence of obvious maternal inheritance, muscle pathological characteristics, or severe complex I deficiency.

Risk to Children When Both Parents Have Alzheimer Disease

Jayadev et alArticle show that of the 111 couples studied with Alzheimer disease (AD), 22.6% of the adult children have developed AD. The diagnosis of AD in these children increases with age, being 31% in those older than 60 years and 41.8% in those older than 70 years.

There is a significant trend in the median age at onset (horizontal bars) in offspring depending on the presence of a family history. With increased “dose” of family history, median age at onset in children of conjugal pairs with Alzheimer disease decreases in a significant trend (*P = .008).

There is a significant trend in the median age at onset (horizontal bars) in offspring depending on the presence of a family history. With increased “dose” of family history, median age at onset in children of conjugal pairs with Alzheimer disease decreases in a significant trend (*P = .008).

Glucocerebrosidase Gene Mutations and Risk for Lewy Body Disease

Mata and colleaguesArticle indicate that mutations in the glucocerebrosidase gene exert a large effect on susceptibility for Lewy body disease.

A New Gene Locus for Primary Lateral Sclerosis

A new locus for a large family with primary lateral sclerosis was identified to chromosome 4ptel-4p16.1.This locus does not map near any other identified locus for upper or lower motor neuron diseases and thus represents a novel locus for primary lateral sclerosis as reported by Valdmanis and colleaguesArticle.

Effectively Treating Tetrahydropterin Synthase Deficiency

Liu and colleaguesArticle were able to achieve considerably higher intelligence quotient scores (mean [SD], 96.7 [9.7]; range, 86-119) for patients with 6-pyruvoyl-tetrahydopterin synthase (PTPS) deficiency by treating them with daily doses of tetrahydrobiopterin replacement (2-4 mg/kg) and levodopa (10-15 mg/kg). The levodopa dose was considerably higher than the typically recommended doses of less than 7 mg/kg/d for patients younger than 2 years and 8 to 10 mg/kg/d for patients 2 years or older. Replacement with 5-hydroxytryptophan therapy varied among patients. An effective newborn screening referral program and early initiation of appropriate therapy preserved the IQ scores of patients with PTPS deficiency.

Hereditary Spastic Paraplegia: Genetic Update

Boukhris et alArticle report that autosomal recessive hereditary spastic paraplegia with thin corpus callosum is a frequent subtype of complicated hereditary spastic paraplegia in Tunisia and is clinically and genetically heterogeneous. SPG11 and SPG15 are the major loci for this entity, and at least another genetic form with unique clinical features exists.