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

• Published in: American journal of human genetics Vol. 67; no. 1; pp. 236 - 243
• Main Authors: Delague, Valérie, Bareil, Corinne, Tuffery, Sylvie, Bouvagnet, Patrice, Chouery, Eliane, Koussa, Salam, Maisonobe, Thierry, Loiselet, Jacques, Mégarbané, André, Claustres, Mireille
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.07.2000; University of Chicago Press; The American Society of Human Genetics
• Subjects: Adolescent; Adult; Age of Onset; Biological and medical sciences; Charcot-Marie-Tooth Disease - epidemiology; Charcot-Marie-Tooth Disease - genetics; Charcot-Marie-Tooth Disease - physiopathology; Child; Child, Preschool; Chromosome Mapping; Chromosomes, Human, Pair 19 - genetics; Consanguinity; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Demyelinating Diseases - epidemiology; Demyelinating Diseases - genetics; Demyelinating Diseases - physiopathology; Disease Progression; Female; Genes, Recessive - genetics; Genetic Heterogeneity; Genetic Markers - genetics; Haplotypes - genetics; Humans; Infant; Infant, Newborn; Islam; Lebanon; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Myelin-Associated Glycoprotein - genetics; Neurology; Pedigree; Lebanon; Genetic mapping; Human; Neuromuscular diseases; Nervous system diseases; Family study; Pathogenesis; Clinical form; Genetic determinism; Genetic disease; Chromosome F19; Phenotype; Gene; Charcot Marie Tooth disease; Autosomal character; Central nervous system disease; Recessive character; Degenerative disease; Consanguinity; Locus; Spinal cord disease; Novelty
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/302980

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 [θ] .00, and a multipoint LOD score of 10.3 for marker D19S881, at θ=.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.