A novel early onset lethal form of catecholaminergic polymorphic ventricular tachycardia maps to chromosome 7p14-p22.
BACKGROUND
Previously, autosomal dominant catecholaminergic polymorphic ventricular tachycardia (CPVT [1]) was mapped to chromosome 1q42-43 with identification of pathogenic mutations in RYR2. Autosomal recessive CPVT (2) was mapped to chromosome 1p13-21, leading to the identification of mutations in CASQ2. In this study, we aimed to elucidate clinical phenotypes of a new variant of CPVT (3) in an inbred Arab family and also delineate the chromosomal location of the gene causing CPVT (3).


RESULTS
In a highly inbred family, clinical symptoms of CPVT appeared early in childhood (7-12 years) and in three of the four cases, the first appearance of symptoms turned into a fatal outcome. Parents of the affected children were first-degree cousins and without any symptoms. Segregation analysis suggested an autosomal recessive inheritance. A genome-wide search using polymorphic DNA markers mapped the disease locus to a 25-Mb interval on chromosome 7p14-p22. A maximal multipoint LOD score of 3.17 was obtained at marker D7S493. Sequencing of putative candidate genes, SP4, NPY, FKBP9, FKBP14, PDE1C, and TBX20, in and around this locus, did not reveal any mutation.


CONCLUSIONS
We have identified a novel highly malignant autosomal recessive form of CPVT and mapped this disorder to a 25-Mb interval on chromosome 7p14-p22.
Bhuiyan
Zahurul A
ZA
Department of Clinical Genetics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. Z.A.Bhuiyan@amc.uva.nl
Hamdan
Mohamed A
MA
Shamsi
Eman T A
ET
Postma
Alex V
AV
Mannens
Marcel M A M
MM
Wilde
Arthur A M
AA
Al-Gazali
Lihadh
L
D000367:Age Factors; D002395:Catecholamines / Q000235:genetics*; D002648:Child; D002874:Chromosome Mapping / Q000379:methods*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics*; D017180:Tachycardia, Ventricular / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality
D002395:Catecholamines