Isolation and characterization of a candidate gene for progressive myoclonus epilepsy on 21q22.3.
The Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1) and autoimmune polyglandular disease type I (APECED) have been mapped to human chromosome 21q22.3 by genetic linkage analysis and/or linkage disequilibrium studies. In order to isolate the genes for these disorders, we have constructed BAC contigs in this region and a 14 week trisomy 21 fetal brain cDNA library. A direct cDNA selection technique, modified to permit the recovery 5' and 3' ends of cDNA, was applied to gene identification using the BAC contigs. We have isolated and characterized a novel gene defined by three overlapping but distinct cDNAs of 5, 3, and 3 kb in size all named EHOC-1 (Epilepsy, HOloprosencephaly Candidate-1). This gene maps less than 45 kb centromeric of D21S25, and spans at least 56 kb of genomic DNA. Northern analysis of the 5 kb cDNA revealed that 8, 7.5 and 5.3 kb transcripts are ubiquitously expressed in adult tissues. DNA sequence analysis of the 5 kb cDNA showed a complete coding sequence of 3570 bp that has multiple putative transmembrane domains and has partial homologies to transmembrane proteins including sodium channel proteins. This gene (EHOC-1) is a good candidate for APECED, and particularly for EPM1 because of the location, size, structure and homologies.
Yamakawa
K
K
Division of Medical Genetics, Cedars-Sinai Medical Center, UCLA 90048-1869, USA.
Mitchell
S
S
Hubert
R
R
Chen
X N
XN
Colbern
S
S
Huo
Y K
YK
Gadomski
C
C
Kim
U J
UJ
Korenberg
J R
JR
D000595:Amino Acid Sequence; D001483:Base Sequence; D001714:Bipolar Disorder / Q000235:genetics; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D018076:DNA, Complementary; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014314:Trisomy
D018076:DNA, Complementary