Novel mutations in the GDAP1 gene in patients affected with early-onset axonal Charcot-Marie-Tooth type 4A.
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.
Moroni
Isabella
I
Division of Child Neurology, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, Milan, Italy. imoroni@istituto-besta.it
Morbin
Michela
M
Milani
Micaela
M
Ciano
Claudia
C
Bugiani
Marianna
M
Pagliano
Emanuela
E
Cavallaro
Tiziana
T
Pareyson
Davide
D
Taroni
Franco
F
D000293:Adolescent; D000367:Age Factors; D017668:Age of Onset; D019943:Amino Acid Substitution / Q000235:genetics; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005121:Extremities / Q000294:innervation / Q000503:physiopathology; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D018908:Muscle Weakness / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010525:Peripheral Nerves / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014826:Vocal Cord Paralysis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
C118663:GDAP protein; D005819:Genetic Markers; D009419:Nerve Tissue Proteins