gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

Various inversions, deletions, and reinsertions on Chromosome 12p in autosomal-dominant hypertension with brachydactyly – a FISH-study in four families and one sporadic case.

Verschiedene Inversionen, Deletionen und Reinsertionen auf Chromosom 12p bei autosomal-dominant vererbtem Bluthochdruck mit Brachydaktylie – eine FISH-Untersuchung an vier Familien und einem sporadischen Patienten

Meeting Abstract

  • M. Kann - Charité Campus Berlin-Buch, HELIOS Klinikum Berlin-Buch (Berlin, D)
  • S. Bähring - Charité Campus Berlin-Buch, HELIOS Klinikum Berlin-Buch (Berlin, D)
  • F.C. Luft - Charité Campus Berlin-Buch, HELIOS Klinikum Berlin-Buch (Berlin, D)
  • M. Kirsch - Friedrich-Alexander-Universität Erlangen-Nürnberg (Erlangen, D)
  • A. Rauch - Friedrich-Alexander-Universität Erlangen-Nürnberg (Erlangen, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP4

The electronic version of this article is the complete one and can be found online at:

Published: August 8, 2006

© 2006 Kann et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



We described a Turkish family with autosomal-dominant, salt-insensitive primary hypertension, and type E brachydactyly. Affected persons die of stroke <50 years of age. Genome-wide linkage analysis disclosed a 10 cM locus on chromosome 12p11.2 (LOD score, 9.29). We sequenced all known genes within the candidate region, but found no mutations. However, interphase fluorescence-in-situ-hybridization (iFISH) studies, using a five-clone BAC array spread across the locus, showed an inversion, deletion, and reinsertion mutation. We now extended iFISH-analysis to three other families and one sporadic case (all non-Turkish), with a 24-clone, contiguous BAC array. We confirmed rearrangements at chromosome 12p in all studied patients. All affected persons had an inversion of the centromeric part of the locus. However, the inversions lacked a common breakpoint and differed greatly in size. In one instance, the locus boundaries were extended. No disruptions of any known coding sequences occurred. Finally, the sporadic case also had a partial deletion of the inverted sequence that was reinserted in the telomeric part of the locus. These findings support a causative role of chromosome 12p rearrangements in the genesis of the hypertension-brachydactyly syndrome. Since no known genes are affected by the mutations, possible causes for the syndrome include as yet unknown genes or non-coding RNA. A position effect must also be considered that could alter the interplay between a regulatory element and its respective gene. We are currently investigating these possibilities.