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 mlcrosateiiite 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 (Z_max=2.63, θ =0.00). in multipoint linkage analysis covering the entire X chromosome, only the region defined by MAOB and DXS991 showed positive iod scores and all other regions showed negative led scores. These data establish the first gene mapping assignment of an X-linked lethal form of human lower motor neuron disease. / 1995 Oxford University Press.