Two novel missense mutations in FGD4/FRABIN cause Charcot-Marie-Tooth type 4H (CMT4H).
By sequencing of the FGD4 coding sequence in a cohort of 101 patients affected by autosomal recessive demyelinating Charcot-Marie-Tooth disease (CMT), we have identified two novel missense mutations in FGD4 in two patients from consanguineous descent: p.Arg442His in an Algerian patient and p.Met566Ile in a Lebanese girl. The patients present early onset, slowly progressive CMT, with drastic reduction of nerve conduction velocities. These mutations are the second and third missense mutations characterized in FGD4. They are likely to lead to conformational changes in the PH1 and FYVE domains.
Inserm, UMR 910, Génétique Médicale et Génomique Fonctionnelle, Faculté de Médecine de la Timone, Marseille, France.
Cécile
C
Baudot
Clothilde
C
Esteve
Christel
C
Castro
Yannick
Y
Poitelon
Camille
C
Mas
Tarik
T
Hamadouche
Maryam
M
El-Rajab
Nicolas
N
Lévy
André
A
Megarbané
Valérie
V
Delague
D000293:Adolescent; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction
C485164:FGD4 protein, human; D008840:Microfilament Proteins