CMT 2B1: Founder Effect and Estimation of the Age of the c.892C>T (p.Arg298Cys)

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Ann Hum Genet. 2008 Jun 11.

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.

Hamadouche T, Poitelon Y, Genin E, Chaouch M, Tazir M, Kassouri N,

Nouioua S, Chaouch A, Boccaccio I, Benhassine T, De Sandre-Giovannoli

A, Grid D, Lévy N, Delague V.

INSERM UMR_S 910, " Génétique Médicale et Génomique Fonctionnelle " ,

Université de La Méditerranée, Faculté de Médecine la Timone,

Marseille, France.

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).