Molecular cloning and analysis of breakpoints on ring chromosome 17 in a patient with autism

• Published in: Gene Vol. 407; no. 1; pp. 186 - 192
• Main Authors: Vazna, Alzbeta, Havlovicova, Marketa, Sedlacek, Zdenek
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.01.2008
• Subjects: Array CGH; Autistic Disorder - genetics; Base Sequence; Chromosome Breakage; Chromosomes, Human, Pair 17 - genetics; Cloning, Molecular; Complex rearrangement; Deletion junction; Female; Humans; Intellectual Disability - genetics; Molecular Sequence Data; Neurofibromatoses - genetics; Non-homologous end joining; Oligonucleotide Array Sequence Analysis; Ring Chromosomes; Sequence Deletion; Terminal deletion; FASPS; Complex rearrangement; non-allelic homologous recombination; long interspersed nucleotide element; CGH; fluorescence in situ hybridisation; SINE; multiplex ligation-dependent probe amplification; short interspersed nucleotide element; familial advanced sleep-phase syndrome; LR-PCR; MLPA; Deletion junction; long-range PCR; Array CGH; LINE; FISH; NAHR; non-homologous end joining; NHEJ; comparative genome hybridisation; Terminal deletion
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2007.10.009

The breakpoint junction on a ring chromosome 17 in a girl with autism, mental retardation, mild dysmorphism and neurofibromatosis was identified and analysed at the nucleotide level. The extent of the deleted segments was about 1.9 Mb on 17p and about 1.0 Mb on 17q. The structure of the junction between the 17p and 17q arms, especially the lack of significant homology between the juxtaposed genomic regions and the presence of short microhomology at the junction site, indicated non-homologous end joining as the most likely mechanism leading to the rearrangement. In addition to the 17p–17q junction itself, a de novo 1 kb deletion in a distance of 400 bp from the junction was identified, which arose most likely as a part of the rearrangement. The defect directly inactivated 3 genes, and the deleted terminal chromosome segments harboured 27 and 14 protein-coding genes from 17p and 17q, respectively. Several of the genes affected by the rearrangement are candidates for the symptoms observed in the patient. Additional rearrangements similar to the 1 kb deletion observed in our patient may remain undetected but can participate in the phenotype of patients with chromosomal aberrations. They can also be the reason for repeated failures to clone breakpoint junctions in other patients described in the literature.