1996 article from New York Times archives explains P0 mutation in Dejerine-Sottas

December 02, 2007

The New York Times recently digitized its pre-Internet archives and opened them to the public, so today I ran a search and found a single mention of Dejerine-Sottas disease. It's an interesting article on the use of x-ray crystallography to shed some light on the proteins created by the P0 mutation, one of the mutations that causes Dejerine-Sottas.

Protein Linked to 3 Nerve Ailments

IN two papers representing the work of 19 researchers, scientists reported last week that they had seen, at a molecular level, the damage to an important protein that is the cause of three genetic nerve disorders. Dr. Thomas Bird, a professor at the University of Washington and chief of neurology at the Veterans Affairs hospital in Seattle, who is not associated with the groups who made the reports, said that the papers are examples of where medicine has arrived: at the molecular detail of human disease.

Read more of Protein Linked to 3 Nerve Ailments

Probing Myelin Protein Zero Gain of Function Mutants

February 24, 2006

Lawrence Wrabetz, Maurizio D'Antonio, Maria Pennuto, Gabriele Dati, Elisa Tinelli, Pietro Fratta, Stefano Previtali, Daniele Imperiale, Jurgen Zielasek, Klaus Toyka, Robin L. Avila, Daniel A. Kirschner, Albee Messing, M. Laura Feltri, and Angelo Quattrini

The P0 glycoprotein is the most abundant protein in myelinated nerves. The extracellular immunoglobulin-like fold forms tetramers in trans that allow for the compaction of myelin layers. Although mutations in myelin protein zero [MPZ], P0) are well-known causes of neuropathy, the clinical phenotypes vary widely, in contrast to the mild abnormalities caused by heterozygous loss of function. Thus Wrabetz et al. explored the hypothesis that MPZ-neuropathies are attributable to gain of function mutations. They examined transgenic mice expressing MPZ mutations at S63, either S63del or S63C. S63del is the mutation underlying an adult-onset demyelinating neuropathy (Charcot-Marie-Tooth, Type 1B [CMT1B]), whereas the S63C mutation causes an early-onset demyelinating neuropathy Déjérine-Sottas syndrome). Both mutant alleles caused a demyelinating neuropathy despite the coexistence of normal alleles, consistent with a gain of function mechanism. S63C caused a packing defect in the myelin, whereas S63C was retained in the endoplasmic reticulum and elicited a presumably toxic unfolded protein response. [From Medical News Today.]

New insights into how genetic mutations arise

October 29, 2005

Researchers at Stanford University have created a larger-than-normal DNA molecule that is copied almost as efficiently as natural DNA.

The findings, reported in the Oct. 25 online edition of the Proceedings of the National Academy of Sciences (PNAS), may reveal new insights into how genetic mutations-tiny mistakes that occur during DNA replication-arise. The discovery was made in the laboratory of Eric Kool, a professor of chemistry at Stanford and co-author of the PNAS study. [Read more]

DNA Machine May Advance Genetic Sequencing for Patients

August 01, 2005

A new kind of machine for decoding DNA may help bring costs so low that it would be feasible to decode an individual's DNA for medical reasons. The machine, developed by 454 Life Sciences of Branford, Conn., was used to resequence the genome of a small bacterium in four hours, its scientists report in an article published online today by the journal Nature.

In 1995, when the same bacterium was first sequenced, by Claire M. Fraser, it required 24,000 separate operations spread over four to six months, she said in an e-mail message. [New York Times]

Drawing with DNA: 'Bioart' illuminates genomics

July 21, 2005

Readers in the Los Angeles area may be interested in the following exhibit at SIGGRAPH 2005:

On any given day, tens of thousands of biologists around the globe run DNA sequences of unknown function through a lightning-fast online algorithm called BLAST - typically submitting 200 to 400 base pairs, or "letters" of genetic code, to be matched against the billions of letters for known genes. Searching for similarities that can shed light on functional or evolutionary relationships, scientists routinely use BLAST to churn through and produce vast amounts of data. Everyday applications include genetic medicine and pharmaceuticals. Yet this process and, more generally, genomics remain dimly understood by the public.

"Ecce Homology," an interactive "bioart" installation to be showcased at SIGGRAPH 2005--in Los Angeles, July 31 through Aug. 4--quite literally makes BLAST and genomics visible. [Medical News Today]

Scientists get the lab laugh with amusing gene names

May 16, 2005

Though not especially informative about the sonic hedgehog gene, this article gives some interesting and amusing insights into the process of naming genes.

Sonic hedgehog makes a protein that sculpts human embryos' nervous system, limbs and organs. Later in life, it can activate hair growth and contribute to several types of cancer. It's hugely interesting to stem cell scientists and oncologists.

But the Norwegian scientist who discovered sonic hedgehog 12 years ago now regrets that it's named after a SEGA video game. He allowed his American collaborators to talk him into adding sonic to the name. The hedgehog part had been decided years before by the irreverent fruit fly scientists.

Clinicopathological and genetic study of early-onset demyelinating neuropathy

October 10, 2004

Bit of bad news here: researchers studied 20 people with Dejerine-Sottas, CMT4 and other related diseases, and found several new mutations.

Abstract from Brain. 2004 Oct 6

Parman Y, Battaloglu E, Baris I, Bilir B, Poyraz M, Bissar-Tadmouri N, Williams A, Ammar N, Nelis E, Timmerman V, De Jonghe P, Necefov A, Deymeer F, Serdaroglu P, Brophy PJ, Said G.

Department of Neurology, Istanbul University, Istanbul Medical Faculty, Turkey.

Summary: Autosomal recessive demyelinating Charcot-Marie-Tooth disease (CMT4), Dejerine-Sottas disease and congenital hypomyelinating neuropathy are variants of hereditary demyelinating neuropathy of infancy, a genetically heterogeneous group of disorders. To explore the spectrum of early-onset demyelinating neuropathies further, we studied the clinicopathological and genetic aspects of 20 patients born to unaffected parents. In 19 families out of 20, consanguinity between the parents or presence of an affected sib suggested autosomal recessive transmission. Screening of various genes known to be involved in CMT4 revealed six mutations of which five are novel. Four of these novel mutations occurred in the homozygous state and include: one in GDAP1, one in MTMR2, one in PRX and one in KIAA1985. One patient was heterozygous for a novel MTMR2 mutation and still another was homozygous for the founder mutation, R148X, in NDRG1. All patients tested negative for mutations in EGR2. Histopathological examination of nerve biopsy specimens showed a severe, chronic demyelinating neuropathy, with onion bulb formation, extensive demyelination of isolated fibres and axon loss. We did not discern a specific pattern of histopathology that could be correlated to mutations in a particular gene.

CMT Research Breakthrough: Function of Periaxin gene now understood

September 10, 2004

Scientists from Edinburgh University have made a breakthrough in developing a treatment for Charcot-Marie-Tooth (CMT) disease. The researchers are now closer to correcting an abnormal gene - Periaxin - that allows nerve insulation to stretch as the nerves get longer when the body grows. If the Periaxin gene is faulty, the insulation, known as myelin, does not lengthen and the nerves cannot conduct impulses quickly, which leads to the muscle-weakening disease developing.

Professor Peter Brophy, director of the centre for neuroscience research at Edinburgh University, was the lead author of the newly published findings, which were the culmination of ten years' work.

He said: "Researchers have now identified about half of the 30 or so different genes responsible for inherited diseases affecting the peripheral nervous system. But developing treatments has been difficult since, for most of these genes, we don?t understand their normal function."

"The Periaxin gene is one of the few for which we now understand its role in nervous system function. The next step is to try to develop gene therapies to correct the abnormal gene carried by patients with this highly disabling disease."

The team of six scientists in Edinburgh have hailed the research as a "significant breakthrough" but are aware much work still lies ahead.

Prof. Brophy said: "We have been looking for the genes responsible and we have found one of them. There hasn't been huge progress in gene therapy so far but there will be in the future. It's good news for sufferers."

It is also thought that the findings could help research into treatments for multiple sclerosis.

Breakthrough in Charcot-Marie-Tooth Research

April 05, 2004

Genetic basis of hereditary nerve disorder revealed

A major form of one of the most prevalent inherited neurological disorders in humans, Charcot-Marie-Tooth disease (CMT), stems from an abnormality in the cellular powerhouses, or mitochondria, that fuel the nerves required for muscle control, suggests new findings by neurogeneticists at the Duke Center for Human Genetics and their international colleagues. The unexpected discovery could open new research pathways to understanding an array of diseases of the peripheral nervous system, as well as treatments for CMT, the researchers said.

Together PCs forecast fold

October 22, 2002

200,000 people donated 2,000 total years of computing time over the past two years in a distributed computing effort to simulate the folding of a single protein.

Trying to anticipate how the many atoms within a protein interact as it crumples up is a mind-bending problem - involving near a billion steps.

Get your Genetic Code Sequenced

September 24, 2002

Despite the fact that scientists still don't fully understand the human genome, orders are already being taken (at $712,000 a pop) to sequence the genes of individuals. The process is expected to take about a week, with the eventual goal of sequencing an individual's genetic makeup in 24 hours for $1,000. I, for one, am looking forward to getting my DNA on a CD. Think of the sci-fi short story possibilities...

Genetics for Dummies

September 16, 2002

Nature Publishing Group has helpfully supplied a User's Guide for the human genome. (Free but tedious registration required... just tell them you're Donald Duck if the questions seem too probing.) So now you know where to look if you're experimenting at home with your chemistry set, and you need to know just how to go about finding genes of interest, or how to find a corresponding genetic sequence in mice.