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 led score was found with DXS991 (Z(max) = 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 led scores, These data establish the first gene mapping assignment of an X-linked lethal form of human lower motor neuron disease.