A recurrent 14q32.2 microdeletion mediated by expanded TGG repeats.
Hum Mol Genet
; 19(10): 1967-73, 2010 May 15.
Article
em En
| MEDLINE
| ID: mdl-20179077
ABSTRACT
Nearly all recurrent microdeletion/duplication syndromes described to date are characterized by the presence of flanking low copy repeats that act as substrates for non-allelic homologous recombination (NAHR) leading to the loss, gain or disruption of dosage sensitive genes. We describe an identical 1.11 Mb heterozygous deletion of 14q32.2 including the DLK1/GTL2 imprinted gene cluster in two unrelated patients. In both patients, the deleted chromosome 14 was of paternal origin, and consistent with this both exhibit clinical features compatible with uniparental disomy (UPD) (14)mat. Using a high-resolution oligonucleotide array, we mapped the breakpoints of this recurrent deletion to large flanking (TGG)(n) tandem repeats, each approximately 500 bp in size and sharing > or =88% homology. These expanded (TGG)(n) motifs share features with known fragile sites and are predicted to form strong guanine quadruplex secondary structures. We suggest that this recurrent deletion is mediated either by NAHR between the TGG repeats, or alternatively results from their inherent instability and/or strong secondary structure. Our results define a recurrent microdeletion of the 14q32.2 imprinted gene cluster mediated by flanking (TGG)(n) repeats, identifying a novel mechanism of recurrent genomic rearrangement. Our observation that expanded repeats can act as catalysts for genomic rearrangement extends the role of triplet repeats in human disease, raising the possibility that similar repeat structures may act as substrates for pathogenic rearrangements genome-wide.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromossomos Humanos Par 14
/
Deleção Cromossômica
/
Expansão das Repetições de Trinucleotídeos
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Newborn
/
Pregnancy
Idioma:
En
Revista:
Hum Mol Genet
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Suíça