AR CMT Type 4 and AR CMT with vocal cord paralysis - from Belgium

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Abstract from Neurology 2002 Dec 24;59(12):1865-1872

Mutations in GDAP1: Autosomal recessive CMT with demyelination and

axonopathy.

Nelis E, Erdem S, Van Den Bergh PY, Belpaire-Dethiou MC, Ceuterick C,

Van Gerwen V, Cuesta A, Pedrola L, Palau F, Gabreels-Festen AA, Verellen

C, Tan E, Demirci M, Van Broeckhoven C, De Jonghe P, Topaloglu H,

Timmerman V.

Molecular Genetics Department (Drs. Nelis, Van Broeckhoven, De Jonghe,

and Timmerman, V. Van Gerwen), Flanders Interuniversity Institute of

Biotechnology, Born-Bunge Foundation, University of Antwerp, Laboratory

of Neuropathology (Dr. Ceuterick), Born-Bunge Foundation, University of

Antwerp, and Department of Neurology (Dr. De Jonghe), University

Hospital Antwerp, Antwerpen, and Centre de Reference Neuromusculaire

(Drs. Van den Bergh and Belpaire-Dethiou), Cliniques Universitaires

St.-Luc, Universite Catholique de Louvain, and Unite de Genetique

Medicale (Dr. Verellen), Universite Catholique de Louvain, Brussels,

Belgium.

BACKGROUND: Mutations in the ganglioside-induced

differentiation-associated protein 1 gene (GDAP1) were recently shown to

be responsible for autosomal recessive (AR) demyelinating

Charcot-Marie-Tooth disease (CMT) type 4A (CMT4A) as well as AR axonal

CMT with vocal cord paralysis.

METHODS: The coding region of GDAP1 was screened for the presence of

mutations in seven families with AR CMT in which the patients were

homozygous for markers of the CMT4A locus at chromosome 8q21.1.

RESULTS: A nonsense mutation was detected in exon 5 (c.581C>G, S194X), a

1-bp deletion in exon 6 (c.786delG, G262fsX284), and a missense mutation

in exon 6 (c.844C>T, R282C).

CONCLUSIONS: Mutations in GDAP1 are a frequent cause of AR CMT. They

result in an early-onset, severe clinical phenotype. The range of nerve

conduction velocities (NCV) is variable. Some patients have normal or

near normal NCV, suggesting an axonal neuropathy, whereas others have

severely slowed NCV compatible with demyelination.

The peripheral nerve biopsy findings are equally variable and show

features of

demyelination and axonal degeneration.

Show:

: Neurology 2002 Dec 24;59(12):1865-1872

Related

Articles, Links

Mutations in GDAP1: Autosomal recessive CMT with

demyelination and axonopathy.

Nelis E, Erdem S, Van Den Bergh PY, Belpaire-Dethiou

MC, Ceuterick

C, Van Gerwen V, Cuesta A, Pedrola L, Palau F,

Gabreels-Festen AA,

Verellen C, Tan E, Demirci M, Van Broeckhoven C, De

Jonghe P,

Topaloglu H, Timmerman V.

Molecular Genetics Department (Drs. Nelis, Van

Broeckhoven, De Jonghe,

and Timmerman, V. Van Gerwen), Flanders Interuniversity

Institute of

Biotechnology, Born-Bunge Foundation, University of

Antwerp, Laboratory

of Neuropathology (Dr. Ceuterick), Born-Bunge

Foundation, University of

Antwerp, and Department of Neurology (Dr. De Jonghe),

University Hospital

Antwerp, Antwerpen, and Centre de Reference

Neuromusculaire (Drs. Van

den Bergh and Belpaire-Dethiou), Cliniques

Universitaires St.-Luc, Universite

Catholique de Louvain, and Unite de Genetique Medicale

(Dr. Verellen),

Universite Catholique de Louvain, Brussels, Belgium.

BACKGROUND: Mutations in the ganglioside-induced

differentiation-associated protein 1 gene (GDAP1) were

recently shown to be

responsible for autosomal recessive (AR) demyelinating

Charcot-Marie-Tooth

disease (CMT) type 4A (CMT4A) as well as AR axonal CMT

with vocal cord

paralysis. METHODS: The coding region of GDAP1 was

screened for the

presence of mutations in seven families with AR CMT in

which the patients

were homozygous for markers of the CMT4A locus at

chromosome 8q21.1.

RESULTS: A nonsense mutation was detected in exon 5

(c.581C>G, S194X),

a 1-bp deletion in exon 6 (c.786delG, G262fsX284), and

a missense mutation

in exon 6 (c.844C>T, R282C). CONCLUSIONS: Mutations in

GDAP1 are a

frequent cause of AR CMT. They result in an

early-onset, severe clinical

phenotype. The range of nerve conduction velocities

(NCV) is variable. Some

patients have normal or near normal NCV, suggesting an

axonal neuropathy,

whereas others have severely slowed NCV compatible with

demyelination.

The peripheral nerve biopsy findings are equally

variable and show features of

demyelination and axonal degeneration.