Genotype-phenotype analysis of Jervell and Lange-Nielsen syndrome in six families from Saudi Arabia.
PMID 24372464 | DOI 10.1111/cge.12330 · Clinical genetics · 2015 · View on PubMed ↗
We sought to explore the genotype-phenotype of Jervell and Lange-Nielsen syndrome (JLNS) patients in Saudi Arabia. We have also assessed the plausible effect of consanguinity into the pathology of JLNS. Six families with at least one JLNS-affected member attended our clinic between 2011 and 2013. Retrospective and prospective clinical data were collected and genetic investigation was performed. Pathogenic mutations in the KCNQ1 gene were detected in all JLNS patients. The homozygous mutations detected were Leu273Phe, Asp202Asn, Ile567Thr, and c.1486_1487delCT and compound heterozygous mutations were c.820_ 830del and c.1251+1G>T. All living JLNS patients except one had a QTc of >500 ms and a history of recurrent syncope. β-Blockers abolished the cardiac-related events in all patients except two siblings with homozygous Ile567Thr mutation. Four of the six mutations were originally reported in autosomal dominant long QT syndrome (LQTS) patients. Eighty percent of the heterozygote mutation carriers showed prolongation of QTc, but majority of these reported no symptoms attributable to arrhythmias. Mutations detected in this study will be advantageous in tribe and region-specific cascade screening of LQTS in Saudi Arabia.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | KCNQ1 | “Pathogenic mutations in the KCNQ1 gene were detected in all JLNS patients.” | 0.98 | hgnc_dict_v1 |
| phenotype | long QT syndrome | “Four of the six mutations were originally reported in autosomal dominant long QT syndrome (LQTS) patients.” | 0.98 | phenotype_alias_lexicon_v2 |
| phenotype | arrhythmia | “Eighty percent of the heterozygote mutation carriers showed prolongation of QTc, but majority of these reported no symptoms attributable to arrhythmias.” | 0.93 | phenotype_alias_lexicon_v2 |
| population | Saudi Arabia | “Genotype-phenotype analysis of Jervell and Lange-Nielsen syndrome in six families from Saudi Arabia. We sought to explore the genotype-phenotype of Jervell and Lange-Nielsen syndrome (JLNS) patients in Saudi Arabia. We have also assessed the plausible effect of consanguinity into the pathology of JLNS. Mutations detected in this study will be advantageous in tribe and region-specific cascade screening of LQTS in Saudi Arabia.” | 0.95 | saudi_context_rules_v1 |
| variant | c.1486_1487delCT | “The homozygous mutations detected were Leu273Phe, Asp202Asn, Ile567Thr, and c.1486_1487delCT and compound heterozygous mutations were c.820_ 830del and c.1251+1G>T.” | 0.95 | hgvs_regex_v1 |
| variant | c.1251+1G>T | “The homozygous mutations detected were Leu273Phe, Asp202Asn, Ile567Thr, and c.1486_1487delCT and compound heterozygous mutations were c.820_ 830del and c.1251+1G>T.” | 0.95 | hgvs_regex_v1 |