Back to Search
Start Over
Presence of ATM protein and residual kinase activity correlates with the phenotype in ataxia-telangiectasia: a genotype-phenotype study.
- Source :
-
Human mutation [Hum Mutat] 2012 Mar; Vol. 33 (3), pp. 561-71. Date of Electronic Publication: 2012 Jan 25. - Publication Year :
- 2012
-
Abstract
- Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder with multisystem involvement and cancer predisposition, caused by mutations in the A-T mutated (ATM) gene. To study genotype-phenotype correlations, we evaluated the clinical and laboratory data of 51 genetically proven A-T patients, and additionally measured ATM protein expression and kinase activity. Patients without ATM kinase activity showed the classical phenotype. The presence of ATM protein, correlated with slightly better immunological function. Residual kinase activity correlated with a milder and essentially different neurological phenotype, absence of telangiectasia, normal endocrine and pulmonary function, normal immunoglobulins, significantly lower X-ray hypersensitivity in lymphocytes, and extended lifespan. In these patients, cancer occurred later in life and generally consisted of solid instead of lymphoid malignancies. The genotypes of severely affected patients generally included truncating mutations resulting in total absence of ATM kinase activity, while patients with milder phenotypes harbored at least one missense or splice site mutation resulting in expression of ATM with some kinase activity. Overall, the phenotypic manifestations in A-T show a continuous spectrum from severe classical childhood-onset A-T to a relatively mild adult-onset disorder, depending on the presence of ATM protein and kinase activity. Each patient is left with a tremendously increased cancer risk.<br /> (© 2011 Wiley Periodicals, Inc.)
- Subjects :
- Adolescent
Adult
Ataxia Telangiectasia genetics
Ataxia Telangiectasia Mutated Proteins
Cell Cycle Proteins genetics
Child
DNA-Binding Proteins genetics
Female
Genetic Association Studies
Humans
Male
Middle Aged
Protein Serine-Threonine Kinases genetics
Tumor Suppressor Proteins genetics
Young Adult
Ataxia Telangiectasia metabolism
Ataxia Telangiectasia pathology
Cell Cycle Proteins metabolism
DNA-Binding Proteins metabolism
Protein Serine-Threonine Kinases metabolism
Tumor Suppressor Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-1004
- Volume :
- 33
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Human mutation
- Publication Type :
- Academic Journal
- Accession number :
- 22213089
- Full Text :
- https://doi.org/10.1002/humu.22016