Neurofilament light chain polypeptide gene mutations in CMT: nonsense mutation

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J Hum Genet. 2009 Jan 16. [Epub ahead of print]

Neurofilament light chain polypeptide gene mutations in Charcot-Marie-

Tooth disease: nonsense mutation probably causes a recessive

phenotype.

Abe A, Numakura C, Saito K, Koide H, Oka N, Honma A, Kishikawa Y,

Hayasaka K.

1Department of Pediatrics, Yamagata University School of Medicine,

Yamagata, Japan.

The neurofilament light chain polypeptide (NEFL) forms the major

intermediate filament in neurons and axons. NEFL mutation is a cause

of axonal or demyelinating forms of dominant Charcot-Marie-Tooth

disease (CMT). We investigated NEFL in 223 Japanese CMT patients who

were negative for PMP22, MPZ, GJB1, LITAF, EGR2, GDAP1, MTMR2 and PRX

in the demyelinating form and negative for MFN2, MPZ, GJB1, HSP27,

HSP22 and GARS in the axonal form.

We detected four heterozygous missense mutations-Pro8Leu, Glu90Lys,

Asn98Ser and Glu396Lys--in five unrelated patients and a homozygous

nonsense mutation, Glu140Stop, in one other patient. All patients had

mildly to moderately delayed nerve conduction velocities, possibly

caused by a loss of large diameter fibers.

This is the first report of a homozygous nonsense mutation of NEFL.

Results of our study show that nonsense NEFL mutations probably cause

a recessive phenotype, in contrast to missense mutations, which cause

a dominant phenotype.