Clinical and Genetic Analysis of Long QT Syndrome in Children from Six Families in Saudi Arabia: Are They Different?

Bhuiyan, Zahurul A.; Al-Shahrani, Safar; Al‐Khadra, Ayman S.; Al-Ghamdi, Saleh; AlKhalaf, K.; Mannens, Marcel M.A.M.; Wilde, Arthur A.M.; Momenah, Tarek

doi:10.1007/s00246-008-9377-y

Cited by 11 publications

(21 citation statements)

References 47 publications

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“…In the Netherlands, so far, we do not seem to have clear LQTS founder mutations, with the exception of the p. Tyr1795_Glu1796insAsp in the SCN5A gene [20,21]. However, LQTS-causing founder mutations have been discovered in other parts of the world, i.e., South Africa, Sweden, Saudi Arabia, and Finland [10][11][12][13][14][15][16]. An example is the p.Ala341Val mutation, identified in at least 22 LQT1 families in South Africa.…”

Section: Discussionmentioning

confidence: 93%

“…c Disparity of the p.Ile1768Val mutation in SCN5A rather benign, similar to the reported Swedish founder mutation. The intron mutation c.387-5>A in KCNQ1 and the p.Gln1070X mutation in KCNH2, both found homozygously in consanguineous, but apparently unrelated, Saudi Arabian families, appeared to be founders as well, since both families had identical haplotypes [16]. In these families, there are several severely affected individuals due to homozygous mutation carriership.…”

Section: Discussionmentioning

confidence: 97%

“…In this manuscript, as part of a series on Dutch founder mutations and recurrent mutations in inherited diseases, we present an overview of the yield of the molecular genetic tests performed in index cases (probands) with a definite or suspected LQTS in the Netherlands. In a number of countries, including Finland, Sweden, Saudi Arabia, and South Africa, LQTS founder mutations have been described, i.e., single mutations occurring within several families which originate from common ancestors (the "founder") [10][11][12][13][14][15][16]. However, in general, LQTS is regarded as a disease where each family has its own "private" mutation [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

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Recurrent and Founder Mutations in the Netherlands: the Long-QT Syndrome*

Hofman¹,

Jongbloed²,

Postema³

et al. 2013

De Nederlandse Gezondheidszorg

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Hofman, N.; Jongbloed, R.; Postema, P.G.; Nannenberg, E.; Alders, M.; Wilde, A.A.M. Published in: Cardiologie DOI:10.1007/s12471-010-0046-4 Link to publication Citation for published version (APA):Hofman, N., Jongbloed, R., Postema, P. G., Nannenberg, E., Alders, M., & Wilde, A. A. M. (2011). Recurrent and Founder Mutations in the Netherlands: the Long-QT Syndrome. Cardiologie, 19(1), 10-16. DOI: 10.1007/s12471-010-0046-4 General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. AbstractBackground 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 haplotype-sharing of the mutation carriers is pertinent to provide more evidence for founder mutation-based LQTS pathology in our country.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Recurrent and Founder Mutations in the Netherlands: the Long-QT Syndrome*

Hofman¹,

Jongbloed²,

Postema³

et al. 2013

De Nederlandse Gezondheidszorg

View full text Add to dashboard Cite

show abstract

“…In the Netherlands, so far, we do not seem to have clear LQTS founder mutations, with the exception of the p.Tyr1795_Glu1796insAsp in the SCN5A gene [20, 21]. However, LQTS-causing founder mutations have been discovered in other parts of the world, i.e., South Africa, Sweden, Saudi Arabia, and Finland [10–16]. An example is the p.Ala341Val mutation, identified in at least 22 LQT1 families in South Africa.…”

Section: Discussionmentioning

confidence: 99%

“…In this manuscript, as part of a series on Dutch founder mutations and recurrent mutations in inherited diseases, we present an overview of the yield of the molecular genetic tests performed in index cases (probands) with a definite or suspected LQTS in the Netherlands. In a number of countries, including Finland, Sweden, Saudi Arabia, and South Africa, LQTS founder mutations have been described, i.e., single mutations occurring within several families which originate from common ancestors (the “founder”) [10–16]. However, in general, LQTS is regarded as a disease where each family has its own “private” mutation [17–19].…”

Section: Introductionmentioning

confidence: 99%

Recurrent and Founder Mutations in the Netherlands: the Long-QT Syndrome

et al. 2010

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Background and objectiveThe 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.MethodsBy 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.ResultsWe 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.ConclusionWhereas 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 haplotype-sharing of the mutation carriers is pertinent to provide more evidence for founder mutation-based LQTS pathology in our country.

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Long QT syndrome mutation detection by SNaPshot technique

et al. 2011

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Long QT syndrome (LQTS) is a cardiac disorder with an abnormality of cardiac rhythm associated with sudden death especially in younger, apparently healthy individuals. If there is no clear cause of death detectable during comprehensive coroner's inquest (autopsy-negative cases), you have to consider LQTS and other heritable arrhythmia syndromes. A molecular genetic screening regarding mutations in associated genes can help to ensure the cause of death and to protect affected family members. Genetic testing of LQTS, currently performed mainly by sequencing, is still very expensive and time consuming. With this study we present a rapid and reasonable method for the simultaneously screening of some of the most common mutations associated with LQTS, focused on the KCNQ1 and KCNH2 genes. With the method of SNaPshot minisequencing, a total of 58 mutations were analyzed in four multiplex assays which were successfully established and optimized. The comparison with samples previously analyzed by direct sequencing showed concordance. Furthermore, autopsy-negative cases were tested but no mutations could be observed in any of the specimen. The presented method is well suitable for LQTS mutation screening. An enhancement to further mutations and population-based investigations regarding mutation frequencies should be the aim of prospective studies.

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Clinical and Genetic Analysis of Long QT Syndrome in Children from Six Families in Saudi Arabia: Are They Different?

Cited by 11 publications

References 47 publications

Recurrent and Founder Mutations in the Netherlands: the Long-QT Syndrome*

Recurrent and Founder Mutations in the Netherlands: the Long-QT Syndrome*

Recurrent and Founder Mutations in the Netherlands: the Long-QT Syndrome

Long QT syndrome mutation detection by SNaPshot technique

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