PT - JOURNAL ARTICLE AU - Tiia M Luukkonen AU - Minna Pöyhönen AU - Aarno Palotie AU - Pekka Ellonen AU - Sonja Lagström AU - Joseph H Lee AU - Joseph D Terwilliger AU - Riitta Salonen AU - Teppo Varilo TI - A balanced translocation truncates Neurotrimin in a family with intracranial and thoracic aortic aneurysm AID - 10.1136/jmedgenet-2012-100977 DP - 2012 Oct 01 TA - Journal of Medical Genetics PG - 621--629 VI - 49 IP - 10 4099 - http://jmg.bmj.com/content/49/10/621.short 4100 - http://jmg.bmj.com/content/49/10/621.full SO - J Med Genet2012 Oct 01; 49 AB - Background Balanced chromosomal rearrangements occasionally have strong phenotypic effects, which may be useful in understanding pathobiology. However, conventional strategies for characterising breakpoints are laborious and inaccurate. We present here a proband with a thoracic aortic aneurysm (TAA) and a balanced translocation t(10;11) (q23.2;q24.2). Our purpose was to sequence the chromosomal breaks in this family to reveal a novel candidate gene for aneurysm. Methods and results Intracranial aneurysm (IA) and TAAs appear to run in the family in an autosomal dominant manner: After exploring the family history, we observed that the proband's two siblings both died from cerebral haemorrhage, and the proband's parent and parent's sibling died from aortic rupture. After application of a genome-wide paired-end DNA sequencing method for breakpoint mapping, we demonstrate that this translocation breaks intron 1 of a splicing isoform of Neurotrimin at 11q25 in a previously implicated candidate region for IAs and AAs (OMIM 612161). Conclusions Our results demonstrate the feasibility of genome-wide paired-end sequencing for the characterisation of balanced rearrangements and identification of candidate genes in patients with potentially disease-associated chromosome rearrangements. The family samples were gathered as a part of our recently launched National Registry of Reciprocal Balanced Translocations and Inversions in Finland (n=2575), and we believe that such a registry will be a powerful resource for the localisation of chromosomal aberrations, which can bring insight into the aetiology of related phenotypes.