24 research outputs found
A modified multiplex ligation-dependent probe amplification method for the detection of 22q11.2 copy number variations in patients with congenital heart disease
Tetrasomy 3q26.32-q29 due to a supernumerary marker chromosome in a child with pigmentary mosaicism of Ito
The analysis of chromosomal abnormalities in patients with recurrent pregnancy loss, focusing on the prognosis of patients with inversion of chromosome (9)
Falciform Macular Folds and Chromosome 22q11.2: Evidence in Support of a Locus for Familial Exudative Vitreoretinopathy (FEVR)
Predominance of Null Mutations in Ataxia-Telangiectasia
Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, AIM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a PI 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the PI 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the AIM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T.WoSScopu