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Ataxia-telangiectasia (AT) is a human autosomal recessive disorder of childhood characterized by: (1) progressive cerebellar ataxia with degeneration of Purkinje cells; (2) hypersensitivity of fibroblasts and lymphocytes to ionizing radiation; (3) a 61-fold and 184-fold increased cancer incidence in white and black patients, respectively; (4) non-random chromosomal rearrangements in lymphocytes; (5) thymic hypoplasia with cellular and humoral (IgA and IgG2) immunodeficiencies; (6) elevated serum level of alphafetoprotein; (7) premature ageing; and (8) endocrine disorders, such as insulin-resistant diabetes mellitus. A DNA processing or repair protein is the suspected common denominator in this pathology. Heterozygotes are generally healthy; however, the sensitivity of their cultured cells to ionizing radiation is intermediate between normal individuals and that of affected homozygotes. Furthermore, heterozygous females are at an increased risk of breast cancer. These findings, when coupled with an estimated carrier frequency of 0.5-5.0%, suggest that (1) as many as one in five women with breast cancer may carry the AT gene and that (2) the increased radiation sensitivity of AT heterozygotes may be causing radiation therapists to reduce the doses of radiation used for treating cancer in all patients. To identify the genetic defect responsible for this multifaceted disorder, and to provide effective carrier detection, we performed a genetic linkage analysis of 31 families with AT-affected members. This has allowed us to localize a gene for AT to chromosomal region 11q22-23.
R A Gatti, and
I Berkel, and
E Boder, and
G Braedt, and
P Charmley, and
P Concannon, and
F Ersoy, and
T Foroud, and
N G Jaspers, and
K Lange
January 1991,
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R A Gatti, and
I Berkel, and
E Boder, and
G Braedt, and
P Charmley, and
P Concannon, and
F Ersoy, and
T Foroud, and
N G Jaspers, and
K Lange
July 1992,
FASEB journal : official publication of the Federation of American Societies for Experimental Biology,
R A Gatti, and
I Berkel, and
E Boder, and
G Braedt, and
P Charmley, and
P Concannon, and
F Ersoy, and
T Foroud, and
N G Jaspers, and
K Lange
August 1999,
Neuropediatrics,
R A Gatti, and
I Berkel, and
E Boder, and
G Braedt, and
P Charmley, and
P Concannon, and
F Ersoy, and
T Foroud, and
N G Jaspers, and
K Lange
February 1993,
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R A Gatti, and
I Berkel, and
E Boder, and
G Braedt, and
P Charmley, and
P Concannon, and
F Ersoy, and
T Foroud, and
N G Jaspers, and
K Lange
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R A Gatti, and
I Berkel, and
E Boder, and
G Braedt, and
P Charmley, and
P Concannon, and
F Ersoy, and
T Foroud, and
N G Jaspers, and
K Lange
December 1994,
International journal of radiation biology,
R A Gatti, and
I Berkel, and
E Boder, and
G Braedt, and
P Charmley, and
P Concannon, and
F Ersoy, and
T Foroud, and
N G Jaspers, and
K Lange
July 1994,
Genomics,
R A Gatti, and
I Berkel, and
E Boder, and
G Braedt, and
P Charmley, and
P Concannon, and
F Ersoy, and
T Foroud, and
N G Jaspers, and
K Lange
June 1994,
Genomics,
R A Gatti, and
I Berkel, and
E Boder, and
G Braedt, and
P Charmley, and
P Concannon, and
F Ersoy, and
T Foroud, and
N G Jaspers, and
K Lange
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Human genetics,
R A Gatti, and
I Berkel, and
E Boder, and
G Braedt, and
P Charmley, and
P Concannon, and
F Ersoy, and
T Foroud, and
N G Jaspers, and
K Lange
July 1993,
Genomics,
