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Seven novel mutations in the adenosine deaminase (ADA) gene in patients with severe and delayed onset combined immunodeficiency: G74C, V129M, G140E, R149W, Q199P, 462delG, and E337del
Author(s) -
ArredondoVega FX,
Santisteban I,
Notarangelo LD,
Dahr J. El,
Buckley R,
Roifman C,
Conley ME,
Hershfield MS
Publication year - 1998
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1998)11:6<482::aid-humu14>3.0.co;2-h
Subject(s) - missense mutation , biology , adenosine deaminase , severe combined immunodeficiency , allele , adenosine deaminase deficiency , compound heterozygosity , mutation , immunodeficiency , heterozygote advantage , genotype , phenotype , immune system , age of onset , genetics , primary immunodeficiency , gene , immunology , medicine , adenosine , endocrinology , disease
The degree of immunodeficiency associated with deficiency of adenosine deaminase (ADA) is variable. Most patients are infants with severe combined immunodeficiency (SCID), but in about 20 percent immune dysfunction becomes manifest later in childhood ("delayed‐onset"); several patients with "late" or "adult" onset of immune dysfunction have been diagnosed at 15–39 years. Over 40 ADA gene mutations have thus far been identified. To better define the genotype‐phenotype relationship, we report 7 novel ADA mutations, including 5 missense mutations (G74C, V129M, G140E, R149W, Q199P) and two short deletions (462delG, E337del). These were identifed among 7 patients (3 with SCID and 4 with delayed‐onset). A homozygote for 462delG had SCID, whereas patients homozygous or heterozygous for V129M had delayed‐onset. Two other delayed‐onset patients, one heterozygous for G74C and the other for Q199P, each had a second allele carrying the previously reported "severe" mutation G216R. These findings are consistent with previous observations suggesting that, in general, SCID occurs when both alleles eliminate ADA function, and a milder phenotype when at least one allele can supply a low level of function. Hum Mutat 11:482, 1998. © 1998 Wiley‐Liss, Inc.