Abstract
The 1p36 deletion syndrome is 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 chromosome and P1-derived artificial chromosome genomic
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-bands by trypsin using
Giemsa (GTG), but FISH screening with 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 map and 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 retardation and congenital heart defects.
Although haploinsufficiency of 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.
Keywords
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Article info
Publication history
Accepted:
February 10,
2005
Received in revised form:
February 10,
2005
Received:
August 19,
2003
Footnotes
☆The Paper is based on the Lecture given at the Sixth Annual Meeting of the Infantile Seizure Society, Tokyo, March 15–16, 2003.
Identification
Copyright
© 2005 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
