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Confirmation of linkage in X‐linked infantile spasms (West syndrome) and refinement of the disease locus to Xp21.3‐Xp22.1
Author(s) -
Bruyere Helene,
Lewis ME Suzanne,
Wood Stephen,
MacLeod Patrick J,
Langlois Sylvie
Publication year - 1999
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1034/j.1399-0004.1999.550305.x
Subject(s) - locus (genetics) , genetics , genetic linkage , x chromosome , linkage (software) , biology , medicine , gene
The syndrome of infantile spasms, hypsarrhythmia, and mental retardation (West 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 have identified a multi‐generation family from Western Canada with this rare syndrome of infantile spasms, seen exclusively in male offspring from asymptomatic mothers, thereby confirming segregation as an X‐linked recessive trait. Using highly polymorphic microsatellite CA‐repeat probes evenly distributed over the entire X chromosome, linkage to markers DXS7110, DXS989, DXS1202, and DXS7106 was confirmed, with a maximum LOD score of 3.97 at a Θ of 0.0. The identification of key recombinants refined the disease‐containing interval between markers DXS1226 and the adrenal hypoplasia locus (AHC). This now maps the X‐linked infantile spasms gene locus to chromosome Xp21.3‐Xp22.1 and refines the interval containing the candidate gene to 7.0 cM. Furthermore, this interval overlaps several loci previously linked with either syndromic or non‐syndromic X‐linked mental retardation (XLMR), including one 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 the critical interval defined between Xp21.3‐Xp22.1.