Clinical spectrum of CMT4C disease in patients homozygous for the p.Arg1109X mutation in SH3TC2.
We investigated the manifestations of CMT4C disease in a genetically homogeneous group of patients homozygous for the recently identified Gypsy founder mutation p.Arg1109X in SH3TC2. We observed a surprising degree of variation in age at onset, rate of progression, extent and severity of motor and sensory involvement, scoliosis, and cranial nerve involvement, suggesting that the phenotypic spectrum of CMT4C disease is much broader than the classical diagnostic criteria. Phenotype similarity in first degree relatives and increasing heterogeneity in more distantly related subjects point to the involvement of genetic modifiers, possibly variants in the genes encoding protein partners interacting with SH3TC2.
Colomer
Jaume
J
Servei de Neurologia, Hospital Sant Joan de Déu, Barcelona, Spain.
Gooding
Rebecca
R
Angelicheva
Dora
D
King
Rosalind H M
RH
Guillén-Navarro
Encarna
E
Parman
Yesim
Y
Nascimento
Andres
A
Conill
Joan
J
Kalaydjieva
Luba
L
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D018703:Founder Effect; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D011506:Proteins / Q000235:genetics*; D006178:Romani People / Q000235:genetics*
D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C488620:SH3TC2 protein, human