Novel mental retardation-epilepsy syndrome linked to Xp21.1-p11.4.
We evaluated a kindred with X-linked mental retardation and epilepsy. Seven affected males with mild to moderate mental retardation developed seizures (primarily generalized, tonic-clonic, and atonic) that began on average at 6.8 months of age (range, 4 to 14 months). These patients did not have a history of infantile spasms. There were no dysmorphic features. Other than mental retardation, the neurological examination was unremarkable, with exception of 2 affected subjects who had mild generalized rigidity and ataxia. We identified tight linkage to a group of markers on Xp21.1-p11.4. A maximum two-point LOD score of +3.83 at straight theta = 0 was obtained for markers DXS8090, DXS1069, DXS8102, and DXS8085. This locus spans 7.7cM between DXS1049 and DXS8054 and does not overlap the locus for X-linked West syndrome. The tetraspanin gene, implicated in nonspecific mental retardation, is mapped to this region. We sequenced the tetraspanin coding sequence in subjects with X-linked mental retardation and epilepsy and did not identify disease-specific mutations. The syndrome we describe, designated X-linked mental retardation and epilepsy, is clinically and genetically distinct from X-linked West syndrome and other X-linked mental retardation-epilepsy syndromes.
Hedera
Peter
P
Department of Neurology, University of Michigan, Ann Arbor, USA.
Alvarado
David
D
Beydoun
Ahmad
A
Fink
John K
JK
D000293:Adolescent; D000328:Adult; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D004569:Electroencephalography; D004576:Electromyography; D004827:Epilepsy / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005192:Family Health; D005260:Female; D020233:Gait Disorders, Neurologic / Q000150:complications; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009431:Neural Conduction; D010375:Pedigree; D012600:Scoliosis / Q000150:complications; D059470:Tetraspanins; D014960:X Chromosome
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C512650:TSPAN2 protein, human; D059470:Tetraspanins