Two Novel Mutations in the GDAP1 and PRX Genes in Early Onset CMT

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Neuropediatrics. 2008 Feb;39(1):33-8.

Two Novel Mutations in the GDAP1 and PRX Genes in Early Onset Charcot-

Marie-Tooth Syndrome.

Auer-Grumbach M, Fischer C, Papiæ L, E, Plecko B, Bittner RE,

Bernert G, Pieber TR, Miltenberger G, Schwarz R, Windpassinger C,

Grill F, Timmerman V, Speicher MR, Janecke AR.

1Institute of Human Genetics, Medical University of Graz, Austria.

Autosomal recessive Charcot-Marie-Tooth syndrome (AR-CMT) is often

characterised by an infantile disease onset and a severe phenotype.

Mutations in the ganglioside-induced differentiation-associated

protein 1 ( GDAP1) gene are thought to be a common cause of AR-CMT.

Mutations in the periaxin ( PRX) gene are rare. They are associated

with severe demyelination of the peripheral nerves and sometimes lead

to prominent sensory disturbances. T

o evaluate the frequency of GDAP1 and PRX mutations in early onset

CMT, we examined seven AR-CMT families and 12 sporadic CMT patients,

all presenting with progressive distal muscle weakness and wasting.

In one family also prominent sensory abnormalities and sensory ataxia

were apparent from early childhood.

In three families we detected four GDAP1 mutations (L58LfsX4, R191X,

L239F and P153L), one of which is novel and is predicted to cause a

loss of protein function. In one additional family with prominent

sensory abnormalities a novel homozygous PRX mutation was found

(A700PfsX17). No mutations were identified in 12 sporadic cases.

This study suggests that mutations in the GDAP1 gene are a common

cause of early-onset AR-CMT. In patients with early-onset

demyelinating AR-CMT and severe sensory loss PRX is one of the genes

to be tested.