title: Mapping of a new locus for autosomal recessive demyelinating Charcot-Marie-Tooth disease to 19q13.1-13.3 in a large consanguineous Lebanese family: exclusion of MAG as a candidate gene.
abstract: Autosomal recessive Charcot-Marie-Tooth disease (CMT) type 4 (CMT4) is a complex group of demyelinating hereditary motor and sensory neuropathies presenting genetic heterogeneity. Five different subtypes that correspond to six different chromosomal locations have been described. We hereby report a large inbred Lebanese family affected with autosomal recessive CMT4, in whom we have excluded linkage to the already-known loci. The results of a genomewide search demonstrated linkage to a locus on chromosome 19q13.1-13.3, over an 8.5-cM interval between markers D19S220 and D19S412. A maximum pairwise LOD score of 5.37 for marker D19S420, at recombination fraction [theta].00, and a multipoint LOD score of 10.3 for marker D19S881, at straight theta = .00, strongly supported linkage to this locus. Clinical features and the results of histopathologic studies confirm that the disease affecting this family constitutes a previously unknown demyelinating autosomal recessive CMT subtype known as "CMT4F." The myelin-associated glycoprotein (MAG) gene, located on 19q13.1 and specifically expressed in the CNS and the peripheral nervous system, was ruled out as being the gene responsible for this form of CMT.
authors.affiliation: Unité de Génétique Médicale, Faculté de Médecine, Université Saint-Joseph, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Delague
authors.forename: C
authors.initials: C
authors.lastname: Bareil
authors.forename: S
authors.initials: S
authors.lastname: Tuffery
authors.forename: P
authors.initials: P
authors.lastname: Bouvagnet
authors.forename: E
authors.initials: E
authors.lastname: Chouery
authors.forename: S
authors.initials: S
authors.lastname: Koussa
authors.forename: T
authors.initials: T
authors.lastname: Maisonobe
authors.forename: J
authors.initials: J
authors.lastname: Loiselet
authors.forename: A
authors.initials: A
authors.lastname: Mégarbané
authors.forename: M
authors.initials: M
authors.lastname: Claustres
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002607:Charcot-Marie-Tooth Disease / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D003241:Consanguinity; D003711:Demyelinating Diseases / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D018740:Genetic Heterogeneity; D005819:Genetic Markers / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007514:Islam; D007861:Lebanon; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D018992:Myelin-Associated Glycoprotein / Q000235:genetics*; D010375:Pedigree
chemical_list: D005819:Genetic Markers; D018992:Myelin-Associated Glycoprotein