title: Novel mutations in the GDAP1 gene in patients affected with early-onset axonal Charcot-Marie-Tooth type 4A.
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.
authors.affiliation: Division of Child Neurology, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, Milan, Italy. imoroni@istituto-besta.it
authors.forename: Isabella
authors.initials: I
authors.lastname: Moroni
authors.forename: Michela
authors.initials: M
authors.lastname: Morbin
authors.forename: Micaela
authors.initials: M
authors.lastname: Milani
authors.forename: Claudia
authors.initials: C
authors.lastname: Ciano
authors.forename: Marianna
authors.initials: M
authors.lastname: Bugiani
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pagliano
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cavallaro
authors.forename: Davide
authors.initials: D
authors.lastname: Pareyson
authors.forename: Franco
authors.initials: F
authors.lastname: Taroni
mesh_terms: 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
chemical_list: C118663:GDAP protein; D005819:Genetic Markers; D009419:Nerve Tissue Proteins