TY - CHAP
T1 - Recurrent and Founder Mutations in the Netherlands
T2 - The Long-QT Syndrome
AU - Hofman, N.
AU - Jongbloed, R.
AU - Postema, P. G.
AU - Nannenberg, E.
AU - Alders, M.
AU - Wilde, A. A. M.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Background and objective The long-QT syndrome (LQTS) is associated with premature sudden cardiac deaths affecting whole families and is caused by mutations in genes encoding for cardiac proteins. When the same mutation is found in different families (recurrent mutations), this may imply either a common ancestor (founder) or multiple de novo mutations. We aimed to review recurrent mutations in patients with LQTS. Methods By use of our databases, we investigated the number of mutations that were found recurrently (at least three times) in LQT type 1-3 patients in the Netherlands. We studied familial links in the apparently unrelated probands, and we visualised the geographical distribution of these probands. Our results were compared with published literature of founder effects in LQTS outside the Netherlands. Results We counted 14 recurrent LQT mutations in the Netherlands. There are 326 identified carriers of one of these mutations. For three of these mutations, familial links were found between apparently unrelated probands. Conclusion Whereas true LQT founder mutations are described elsewhere in the world, we cannot yet demonstrate a real founder effect of these recurrent mutations in the Netherlands. Further studies on the prevalence of these mutations are indicated, and haplotypesharing of the mutation carriers is pertinent to provide more evidence for founder mutation-based LQTS pathology in our country.
AB - Background and objective The long-QT syndrome (LQTS) is associated with premature sudden cardiac deaths affecting whole families and is caused by mutations in genes encoding for cardiac proteins. When the same mutation is found in different families (recurrent mutations), this may imply either a common ancestor (founder) or multiple de novo mutations. We aimed to review recurrent mutations in patients with LQTS. Methods By use of our databases, we investigated the number of mutations that were found recurrently (at least three times) in LQT type 1-3 patients in the Netherlands. We studied familial links in the apparently unrelated probands, and we visualised the geographical distribution of these probands. Our results were compared with published literature of founder effects in LQTS outside the Netherlands. Results We counted 14 recurrent LQT mutations in the Netherlands. There are 326 identified carriers of one of these mutations. For three of these mutations, familial links were found between apparently unrelated probands. Conclusion Whereas true LQT founder mutations are described elsewhere in the world, we cannot yet demonstrate a real founder effect of these recurrent mutations in the Netherlands. Further studies on the prevalence of these mutations are indicated, and haplotypesharing of the mutation carriers is pertinent to provide more evidence for founder mutation-based LQTS pathology in our country.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84931338387&origin=inward
U2 - https://doi.org/10.1007/978-90-368-0705-0_3
DO - https://doi.org/10.1007/978-90-368-0705-0_3
M3 - Chapter
SN - 9036807042
T3 - Founder Mutations in Inherited Cardiac Diseases in the Netherlands
SP - 13
EP - 19
BT - Founder Mutations in Inherited Cardiac Diseases in the Netherlands
PB - Bohn Stafleu Van Loghum
ER -