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

• Published in: Clinical genetics Vol. 55; no. 3; pp. 173 - 181
• Main Authors: Bruyere, Helene, Lewis, ME Suzanne, Wood, Stephen, MacLeod, Patrick J, Langlois, Sylvie
• Format: Journal Article
• Language: English
• Published: Copenhagen Munksgaard International Publishers 01-03-1999; Blackwell
• Subjects: Biological and medical sciences; Chromosome Mapping; DNA - genetics; Family Health; Female; gene localization; Genetic Linkage; Genotype; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; infantile spasms; linkage analysis; Lod Score; Male; Medical sciences; mental retardation; Microsatellite Repeats; Nervous system (semeiology, syndromes); Neurology; Pedigree; Spasms, Infantile - genetics; West syndrome; X chromosome; X Chromosome - genetics; Genetic mapping; Human; Short arm; Nervous system diseases; Linkage; Genetic marker; Family study; Epilepsy; Genetic determinism; West syndrome; Central nervous system disease; Genetics; X-Chromosome; Polymorphism
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1034/j.1399-0004.1999.550305.x

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.