Gene for Progressive Familial Heart Block Type I Maps to Chromosome 19q13

Abstract

The gene for PFHBI maps to an area of approximately 10 cM on chromosome 19q13.2-13.3. There are several candidate genes in this interval; although a recombination event ruled out the myotonic dystrophy locus from direct involvement with PFHBI, the proximity of these two loci may be relevant to the observed cardiac abnormalities of myotonic dystrophy. The results provide a means of DNA-based diagnosis in the families studied and a foundation for cloning studies to identify the causative gene.

Characterisation of the human voltage-gated potassium channel gene, KCNA7, a candidate gene for inherited cardiac disorders, and its exclusion as cause of progressive familial heart block I (PFHBI)

“…The clinical details and pedigrees of the Afrikaner families in which PFHBI segregates were described previously. 4,5 Characterisation of KCNA7 Determining coding sequence A BLAST search of the Genoscope database (http://www.genoscope.org) revealed several 19q13.3 human genomic sequences (eg, R0AA003ZF08G1) that aligned with the published mouse kcna7 cDNA sequence (AF032099). Subsequent BLAST searches of GenBank with this inferred human KCNA7 sequence identified significant matches with human BAC clone BC52309 (synonym: CITB-60B18; GenBank accession no.…”

“…3 Progressive familial heart block type I (PFHBI) is an autosomal dominantly inherited cardiac conduction disorder, which has been mapped to chromosome 19q13.3 in a large South African Afrikaner family. 4 Clinically, PFHBI is characterised by right bundle branch block, left anterior hemiblock, or complete heart block with broad QRS complexes. 5 Evidence of genetic anticipation in this disorder, with an increase in severity of the disease's presentation in succeeding generations, has been reported.…”

“…This member of a multigene family 8 has been mapped by fluorescent in situ hybridisation (FISH) to human chromosome 19q13.3, 7 placing it within the PFHBI locus, where it is flanked by the muscle glycogen synthase gene (GSY1) and histidine-rich calcium binding protein (HRC). 4 The mouse homologue, kcna7, a member of the Shaker-related Kv1-subfamily of K + channels, is abundantly expressed in mouse heart, 7 strengthening the candidacy of the human homologue KCNA7 as the PFHBI-causative gene.…”

Calumenin, a Ca2+-binding Protein Retained in the Endoplasmic Reticulum with a Novel Carboxyl-terminal Sequence, HDEF

“…This region is well conserved between human and mouse, and the syntenic comparison suggests that this region corresponds to human 19q13. 2-13.3 (53), at which the gene for progressive familial heart block type I, autosomal dominantly inherited cardiac bundle-branch disorder, is mapped (54). Since the causal gene of this disease has not been determined so far, further investigation is needed to determine whether the calumenin gene is involved in this disease.…”

Aspects moléculaires de la mort subite de l’adulte

“…Les TV et FV survenant dans un myocarde structurellement anormal peuvent être liées à une dysplasie arythmogène du ventricule droit, pour laquelle plusieurs locus morbides ont été identifiés [8], ou à une cardiomyopathie hypertrophique ou dilatée [9], dont le potentiel arythmogène est bien connu et possiblement lié à une altération de l'énergétique cellulaire [10] Blocs de conduction d'origine génétique Dès les années 1970, les enquêtes familiales réalisées chez des patients porteurs de blocs bifasciculaires ou de bloc complets ont suggéré la participation de facteurs génétiques dans la physiopathologie de formes rares de troubles conductifs [11]. En 1995, un premier locus morbide a été déterminé en 19q13.2-13.3 [12]. Plus récemment, notre laboratoire a identifié le premier gène impliqué dans des troubles conductifs progressifs dont le phénotype est proche de la description classique de la maladie de Lenègre [13,14] …”