Localization of the gene encoding the GABAA receptor beta 3 subunit to the Angelman/Prader-Willi region of human chromosome 15.
Deletions of the proximal long arm of chromosome 15 (bands 15q11q13) are found in the majority of patients with two distinct genetic disorders, Angelman syndrome (AS) and Prader-Willi syndrome (PWS). The deleted regions in the two syndromes, defined cytogenetically and by using cloned DNA probes, are similar. However, deletions in AS occur on the maternally inherited chromosome 15, and deletions in PWS occur on the paternally derived chromosome 15. This observation has led to the suggestion that one or more genes in this region show differential expression dependent on parental origin (genetic imprinting). No genes of known function have previously been mapped to this region. We show here that the gene encoding the GABAA (gamma-aminobutyric acid) receptor beta 3 subunit maps to the AS/PWS region. Deletion of this gene (GABRB3) was found in AS and PWS patients with interstitial cytogenetic deletions. Evidence of beta 3 gene deletion was also found in an AS patient with an unbalanced 13;15 translocation but not in a PWS patient with an unbalanced 9;15 translocation. The localization of this receptor gene to the AS/PWS region suggests a possible role of the inhibitory neurotransmitter GABA in the pathogenesis of one or both of these syndromes.
Wagstaff
J
J
Division of Genetics, Children's Hospital, Boston, MA 02115.
Knoll
J H
JH
Fleming
J
J
Kirkness
E F
EF
Martin-Gallardo
A
A
Greenberg
F
F
Graham
J M
JM
Menninger
J
J
Ward
D
D
Venter
J C
JC
D000595:Amino Acid Sequence; D001259:Ataxia / Q000235:genetics; D001483:Base Sequence; D015139:Blotting, Southern; D002648:Child; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D003001:Cloning, Molecular; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D002658:Developmental Disabilities / Q000235:genetics*; D005091:Exons; D015698:Genomic Library; D006801:Humans; D007845:Laughter; D008214:Lymphocytes / Q000502:physiology; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods; D011218:Prader-Willi Syndrome / Q000235:genetics*; D011963:Receptors, GABA-A / Q000235:genetics*; D015183:Restriction Mapping; D012640:Seizures / Q000235:genetics; D013577:Syndrome
D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D011963:Receptors, GABA-A; D004247:DNA