Severe combined immune deficiency due to a homozygous 3.2-kb deletion spanning the promoter and first exon of the adenosine deaminase gene.
We have investigated the structural gene for adenosine deaminase (ADA) in a female infant with ADA deficiency associated severe combined immune deficiency (ADA-SCID) disease and her family by DNA restriction-fragment-length analysis. In this family a new ADA-specific restriction-fragment-length variant was detected, which involves a 3.2-kb deletion spanning the ADA promoter as well as the first exon. It was found that the patient, who was born to a consanguineous couple, was homozygous and both her parents and her brother were heterozygous for the deletion. No ADA-specific mRNA could be detected by hybridization in fibroblasts derived from this patient. Thus the patient was established to be homozygous for a true null ADA allele. In the light of the apparently normal development of most tissues except the lymphoid tissue the above finding directly questions the classification of ADA as a 'housekeeping' enzyme.
Berkvens
T M
TM
Department of Human Genetics, Sylvius Laboratories, University of Leiden, The Netherlands.
Gerritsen
E J
EJ
Oldenburg
M
M
Breukel
C
C
Wijnen
J T
JT
van Ormondt
H
H
Vossen
J M
JM
van der Eb
A J
AJ
Meera Khan
P
P
D000243:Adenosine Deaminase / Q000097:blood / Q000172:deficiency*; D002872:Chromosome Deletion; D004912:Erythrocytes / Q000201:enzymology; D005091:Exons; D005260:Female; D005796:Genes; D006720:Homozygote; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology / Q000235:genetics*; D007223:Infant; D007962:Leukocytes / Q000201:enzymology; D008297:Male; D009700:Nucleoside Deaminases / Q000172:deficiency*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D014158:Transcription, Genetic
D012333:RNA, Messenger; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase