Founder effect and estimation of the age of the c.892C>T (p.Arg298Cys) mutation in LMNA associated to Charcot-Marie-Tooth subtype CMT2B1 in families from North Western Africa.
CMT2B1, an axonal subtype (MIM 605588) of the Charcot-Marie-Tooth disease, is an autosomal recessive motor and sensory neuropathy characterized by progressive muscular and sensory loss in the distal extremities with chronic distal weakness. The genetic defect associated with the disease is, to date, a unique homozygous missense mutation, p.Arg298Cys (c.892C>T), in the LMNA gene. So far, this mutation has only been found in affected individuals originating from a restricted region of North Western Africa (northwest of Algeria and east of Morocco), strongly suggesting a founder effect. In order to address this hypothesis, genotyping of both STRs and intragenic SNPs was performed at the LMNA locus, at chromosome 1q21.2-q21.3, in 42 individuals affected with CMT2B1 from 25 Algerian families. Our results indicate that the affected individuals share a common ancestral haplotype in a region of about 1.0 Mb (1 cM) and that the most recent common ancestor would have lived about 800-900 years ago (95% confidence interval: 550 to 1300 years).
INSERM UMR_S 910, Génétique Médicale et Génomique Fonctionnelle, Université de La Méditerranée, Faculté de Médecine Timone, Marseille, France.
T
T
Hamadouche
Y
Y
Poitelon
E
E
Genin
M
M
Chaouch
M
M
Tazir
N
N
Kassouri
S
S
Nouioua
A
A
Chaouch
I
I
Boccaccio
T
T
Benhassine
A
A
De Sandre-Giovannoli
D
D
Grid
N
N
Lévy
V
V
Delague
D000462:Algeria; D019943:Amino Acid Substitution; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D006720:Homozygote; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D020080:Tandem Repeat Sequences; D013997:Time Factors
C494847:LMNA protein, human; D034904:Lamin Type A