Severe neuropathy after diphtheria-tetanus-pertussis vaccination in a child carrying a novel frame-shift mutation in the small heat-shock protein 27 gene.
Mutations in small heat-shock protein 27 and small heat-shock protein 22 genes were found in association with Charcot-Marie-Tooth disease type 2 and distal hereditary motor neuropathy. We searched for mutations in small heat-shock protein 27 gene in an Italian family with peripheral neuropathy and intrafamilial phenotypic variability. A novel heterozygous frame-shift mutation c.476_477delCT was found while point mutations in most genes associated with hereditary neuropathies were ruled out. In the proband, who showed a severe early onset peripheral neuropathy, an independent pathogenetic effect on the peripheral nervous system secondary to the tetanus toxoid injection may be supposed. This is the first truncating nonsense mutation in the small heat-shock protein 27 gene identified so far and the clinical, neurophysiologic, and neuropathological findings are discussed.
Mandich
Paola
P
Department of Neurosciences, Ophthalmology and Genetics-Section of Medical Genetics, University of Genova, Genova, Italy.
Grandis
Marina
M
Varese
Alessandra
A
Geroldi
Alessandro
A
Acquaviva
Massimo
M
Ciotti
Paola
P
Gulli
Rossella
R
Doria-Lamba
Laura
L
Fabrizi
Gian Maria
GM
Giribaldi
Gaia
G
Pizzuti
Antonio
A
Schenone
Angelo
A
Bellone
Emilia
E
D017668:Age of Onset; D002675:Child, Preschool; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000009:adverse effects*; D005190:Family; D016368:Frameshift Mutation; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics*; D006360:Heat-Shock Proteins; D006801:Humans; D007558:Italy; D008297:Male; D018832:Molecular Chaperones; D010375:Pedigree; D010523:Peripheral Nervous System Diseases / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D017422:Sequence Analysis, DNA; D013497:Sural Nerve / Q000473:pathology
D015721:Diphtheria-Tetanus-Pertussis Vaccine; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones