NEFL Pro22Arg mutation in CMT disease type 1

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J Hum Genet. 2008 Aug 29.

NEFL Pro22Arg mutation in Charcot Marie Tooth disease type 1.

Shin JS, Chung KW, Cho SY, Yun J, Hwang SJ, Kang SH, Cho EM, Kim SM,

Choi BO.

Department of Neurology and Ewha Medical Research Center, Ewha Womans

University, School of Medicine, Mokdong Hospital, 911-1 Mokdong

Yangcheon-ku, Seoul, 158-710, South Korea.

Charcot-Marie-Tooth disease (CMT) is classified into demyelinating

neuropathy (CMT1) and axonal neuropathy (CMT2). Mutations in the

neurofilament light chain polypeptide (NEFL) gene are present in

CMT2E and CMT1F neuropathies. Two types of Pro22 mutations have been

previously reported: Pro22Ser in CMT2E with giant axons, and Pro22Thr

in CMT1F.

In this study, we identified another Pro22 mutation, Pro22Arg, in a

Korean CMT1 family. An investigation to identify the clinical and

pathological characteristics of the Pro22Arg revealed that it is

associated with demyelinating neuropathy features in CMT1F.

Histopathological findings showed onion bulb formations but no giant

axons. It appears that the Pro22 mutations may influence not only the

Thr-Pro phosphorylation site by proline-directed protein kinases but

also other structural alteration of the NEFL protein in a different

way.