CMT 4A: Novel mutations in the GDAP1 gene in patients affected with early-onset

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Neuromuscular Disorders Volume 19, Issue 7, Pages 476-480 (July 2009)

http://www.nmd-journal.com/article/S0960-8966(09)00119-9/abstract

Novel mutations in the GDAP1 gene in patients affected with early-onset axonal

Charcot-Marie-Tooth type 4A

Isabella Moronia, Michela Morbinb1, Micaela Milanic1, Cianod, nna

Bugiania, Emanuela Paglianoe, Tiziana Cavallarof, e Pareysonc, Franco

Taronic (these authors contributed equally to the manuscript)

Abstract

We report a detailed study of eight patients from four Italian families

presenting with autosomal recessive axonal Charcot-Marie-Tooth disease

(AR-CMT2), characterized by early-onset and progressive severe weakness of all

limbs. Vocal cord paresis was present in two cases. Sural nerve biopsy performed

in three patients showed a severe neuropathy characterized by a predominant

axonal involvement. Five novel mutations (p.Gln99stop, p.Gln122Lys,

p.Arg125stop, p.Val219Asp, p.Asn297Lys) and one previously reported mutation

(p.Leu239Phe) were identified in GDAP1 gene. GDAP1 mutations should be

considered both in recessive and sporadic cases of early-onset axonal CMT.

b Division of Neuropathology, Fondazione IRCCS Istituto Neurologico " Carlo

Besta " , Milan, Italy

c Division of Biochemistry and Genetics, Fondazione IRCCS Istituto Neurologico

" Carlo Besta " , Milan, Italy

d Division of Neurophysiology, Fondazione IRCCS Istituto Neurologico " Carlo

Besta " , Milan, Italy

e Division of Developmental Neurology, Fondazione IRCCS Istituto Neurologico

" Carlo Besta " , Milan, Italy

f Department of Neurological and Visual Sciences, University of Verona, Italy