CMT 2B and 2D research news from MDA

[Guest guest]

New Findings Expected to Improve CMT Diagnosis-from Quest, Vol. 10 No. 3

May/June 2003

Researchers have linked two new genes to Charcot-Marie-Tooth disease

(CMT).

There are over a dozen forms of CMT, many of them traceable to genes

that encode specific components of nerve fibers or myelin, the

protective covering around nerve fibers. The new genes, which bring the

total number of identified CMT genes to 14, appear to have more general

functions.

An MDA-funded team led by Timmerman of the University of Antwerp

in Belgium has found the culprit gene behind CMT type 2B, which causes

such a severe loss of

sensation that wounds to the feet often go unnoticed and rapidly become

infected. The gene, RAB7, encodes a protein that controls the transport

of nutrients and other cargo within cells; it’s not clear why RAB7

defects specifically cause damage to nerve cells.

The same mystery holds for the second new CMT gene: glycyl tRNA

synthetase (GARS), which is part of the machinery that all cells use to

make proteins. A team led by

Green of the National Human Genome Research Institute in Bethesda,

Md., found GARS mutations in families with CMT type 2D and the

clinically similar disease spinal muscular atrophy type 5, both of which

cause pronounced weakness in the upper extremities.

Kumaraswamy Sivakumar, co-director of MDA’s clinic at St. ph’s

Hospital in Phoenix, was part of the CMT2D study, which appears in the

May issue of the American Journal of Human Genetics. Timmerman’s study

appeared in the journal’s April issue.

If current trends continue, each newly discovered CMT gene could lead to

better diagnostic tests for the disease.

Athena Diagnostics (www.athenadiagnostics.com), a company based in

Worcester, Mass., offers a panel of tests for the six genes most often

responsible for CMT, including

periaxin, linked to the disease in early 2001.

In January, MDA grantees Street and Chance of the

University of Washington in Seattle reported that mutations in the LITAF

gene cause CMT type 1C, and

now they’re working toward a genetic test (see " Research Updates, "

March-April). They’ve put out a call for neurologists to help them

identify patients who might have CMT1C.