Confirmation of linkage in X-linked infantile spasms (West syndrome) and refinement of the disease locus to Xp21.3-Xp22.1

The syndrome of infantile spasms, hypsarrhythmia, and mental retardation (W est syndrome) is a classical form of epilepsy, occurring in early infancy, which is etiologically heterogeneous. In rare families, West syndrome is an X-linked recessive condition, mapped to Xp11.-4-Xpter (MIM 308350). We hav e identified a multi-generation family from Western Canada with this rare s yndrome of infantile spasms. seen exclusively in male offspring from asympt omatic mothers, thereby confirming segregation as an X-linked recessive tra it. Using highly polymorphic microsatellite CA-repeat probes evenly distrib uted over the entire X chromosome, linkage to markers DXS7110, DXS989, DXS1 201, and DXS7106 was confirmed, with a maximum LOD score of 3.97 at a 0 of 0.0, The identification of key recombinants refined the disease-containing interval between markers DXS1226 and the adrenal hypoylasia locus (AHC). Th is now maps the X-linked infantile spasms gene locus to chromosome Xp21.3-X p22.1 and refines the interval containing the candidate gene to 7.0 cM. Fur thermore, this interval overlaps several loci previously linked with either syndromic or non-syndromic X-linked mental retardation (XLMR), including o ne recognized locus implicated in neuroaxonal processing (radixin, RDXP2). Collectively, these studies lend strong support for the presence of one or more genes intrinsic to brain development and function, occurring within th e critical interval defined between Xp21.3-Xp22.1.