title: A whole-genome scan in a large family with leukodystrophy and oligodontia reveals linkage to 10q22.
abstract: Dentoleukoencephalopathies with autosomal recessive inheritance are very rare. Recently, a large inbred Syrian pedigree was reported with oligodontia in association with a degenerative neurologic condition characterized by progressive ataxia and pyramidal syndrome and abnormalities in the white matter and cortical atrophy. A whole-genome screening of this family using 382 microsatellite markers was completed, but no evidence was found of linkage to any chromosomal region. A genome-wide linkage analysis using the 260K single nucleotide polymorphism Affymetrix array was then undertaken and a maximum multipoint logarithm of the odds score of 5.66 (NPL score = 7.65) was detected on chromosome 10q22 region. This genomic interval contains 95 known genes including the Prosaposin gene (PSAP) responsible for metachromatic leukodystrophy, which was excluded. Seventeen additional candidate genes were tested and excluded. Sequencing of the whole candidate locus is in progress and should allow the identification of the causative gene in this rare disease, thereby improving the understanding of the physiopathology of this disease.
authors: Unité de Génétique Médicale et laboratoire associé INSERM à l'unité UMR_S 910, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon.
authors: Eliane
authors: E
authors: Chouery
authors: Valérie
authors: V
authors: Delague
authors: Nadine
authors: N
authors: Jalkh
authors: Nabiha
authors: N
authors: Salem
authors: Jessy
authors: J
authors: Kfoury
authors: Diana
authors: D
authors: Rodriguez
authors: Brigitte
authors: B
authors: Chabrol
authors: Odile
authors: O
authors: Boespflug-Tanguy
authors: Nicolas
authors: N
authors: Lévy
authors: Jean Louis
authors: JL
authors: Serre
authors: André
authors: A
authors: Mégarbané
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000848:Anodontia / Q000235:genetics*; D002648:Child; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D005808:Genes, Recessive; D055106:Genome-Wide Association Study; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D013593:Syria