Charcot-Marie-Tooth disease type 1B: marked phenotypic variation of the Ser78Leu mutation in five Italian families.
OBJECTIVE
To describe clinical, electrophysiological and genetic data of five unrelated Sicilian pedigrees harbouring a heterozygous Ser78Leu mutation in the myelin protein zero (MPZ) extracellular domain.


METHODS
Clinical, electrophysiological and genetic findings of 16 patients were reported. Polymorphic markers flanking the coding sequence of MPZ gene were also analysed.


RESULTS
A wide range of age at onset was observed in families 1 and 3, with a clinical heterogeneity, in terms of severity of the disease, within the same family (families 1 and 3), and among families. A markedly unsteady gait was a distinctive feature of many members of family 1. All patients in family 2 complained of severe cramps and painful paresthesia. Molecular genetic analysis showed that all affected subjects shared a common haplotype at three microsatellite loci D1S2858, D1S2624 and D1S484.


CONCLUSIONS
Our study provides further evidence that phenotypic features of MPZ mutations can vary within and among different families. High frequency of Ser78Leu mutation in Sicily as well as the results of haplotype analyses suggest that the mutation may have been inherited from a common ancestor.
Mazzeo
A
A
Department of Neurosciences, Psychiatry and Anaesthesiology University of Messina, Messina, Italy. annamazzeo@yahoo.it
Muglia
M
M
Rodolico
C
C
Toscano
A
A
Patitucci
A
A
Quattrone
A
A
Messina
C
C
Vita
G
G
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics*; D002607:Charcot-Marie-Tooth Disease / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007558:Italy; D007930:Leucine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D018993:Myelin P0 Protein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009431:Neural Conduction / Q000235:genetics; D010375:Pedigree; D010525:Peripheral Nerves / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D012694:Serine / Q000235:genetics; D012720:Severity of Illness Index; D055815:Young Adult
D018993:Myelin P0 Protein; D012694:Serine; D007930:Leucine