Adding insult to injury

A putative splicing factor mutation causes phenotypic variation of an inherited disease

Cathy Holding(cholding@hgmp.mrc.ac.uk)
Aug 14, 2003

Some genetic diseases do not follow a simple pattern of inheritance and exhibit phenotypic variation. This can be explained as a monogenic disorder that is being affected by the action of nonlinked genetic modifiers. A molecular mechanism by which phenotypic variation in disease severity occurs is reported by David Buchner and colleagues at the University of Michigan School of Medicine in the August 15 Science. A mutation in the neuronal sodium channel gene Scn8a results in neurological disease in mice, but the severity varies from progressive but survivable in resistant strains to lethal in susceptible strains, prompting the team to search for a molecular mechanism to account for this in a region they previously mapped to mouse chromosome 3. Comparison of the mouse DNA sequence with the equivalent human region identified a single stop codon mutation that reverse transcription polymerase chain reaction analysis showed to result in both...

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