Epilepsy and neurological findings in 11 individuals with 1p36 deletion syndrome
2005
Abstract The
1p36 deletion syndromeis a newly delineated multiple congenital anomalies/mental retardation syndrome characterized by mental retardation,
growth delay, epilepsy, congenital heart defects, characteristic facial appearance, and
precocious puberty. We analyzed 11 patients by fluorescence in situ hybridization (FISH) using commercially available
bacterial artificial chromosomeand
P1-derived artificial chromosomegenomic clones to define the chromosomal deletion responsible for the
1p36 deletion syndrome. Cytogenetic investigation revealed two cases with a terminal deletion of 1p36. Nine patients had an apparently normal karyotype with standard
G-bandsby trypsin using Giemsa (GTG), but
FISH screeningwith the highly polymorphic genetic marker D1Z2, which is mapped to 1p36.3 and contains an unusual reiterated 40-bp
variable number tandem repeat, revealed a submicroscopic deletion. All patients had severe to
profound mental retardation. Based on the University of California Santa Cruz
Genome Browser, we constructed a
deletion mapand analyzed the relationship between neurological findings and chromosomal deletions for the 11 cases. Six cases had intractable epilepsy and three had no seizures. The common deletion interval was about 1 million base pairs (Mbp) located between RP11-82D16 and RP4-785P20 (Rho guanine exchange factor (GEF) 16). The severity of clinical symptoms correlates with the size of the deletion. This is demonstrated by the 3 patients with at least 8 Mbp deletions that display
profound mental retardationand congenital heart defects. Although
haploinsufficiencyof the potassium channel beta-subunit ( KCNAB2 ) is thought to be responsible for intractable seizures in the
1p36 deletion syndrome, this was not the case for 3 of the 11 patients in this study. Further investigation of the 1p36 region is necessary to allow identification of genes responsible for the
1p36 deletion syndrome.
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