A gene for a severe lethal form of X-linked arthrogryposis (X-linked infantile spinal muscular atrophy) maps to human chromosome Xp11.3-q11.2.
X-linked arthrogryposis Type I (X-linked infantile spinal muscular atrophy) is a rare disorder showing hypotonia, areflexia, and multiple congenital contractures (arthrogryposis) associated with loss of anterior horn cells and death in infancy. We have studied an X-linked arthrogryposis family using highly polymorphic microsatellite markers throughout the X chromosome. Meiotic breakpoint analysis (concordance analysis) based on shared regions of the founder X chromosome was successful in localizing the X-linked arthrogryposis gene to Xp11.3-q11.2. In this region, the highest two-point lod score was found with DXS991 (Zmax = 2.63, theta = 0.00). In multipoint linkage analysis covering the entire X chromosome, only the region defined by MAOB and DXS991 showed positive lod scores and all other regions showed negative lod scores. These data establish the first gene mapping assignment of an X-linked lethal form of human lower motor neuron disease.
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, PA 15261, USA.
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H
Kobayashi
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Baumbach
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Matise
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Schiavi
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Greenberg
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Hoffman
D000293:Adolescent; D001176:Arthrogryposis / Q000235:genetics* / Q000401:mortality; D002675:Child, Preschool; D002874:Chromosome Mapping; D005192:Family Health; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008540:Meiosis; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics*; D014960:X Chromosome