Identification of a novel KCNQ1 mutation in a large Saudi family with long QT syndrome: clinical consequences and preventive implications.
PMID 22708720 | DOI 10.1111/j.1399-0004.2012.01914.x · Clinical genetics · 2013 · View on PubMed ↗
Congenital long QT syndrome (LQTS) is an inherited potentially fatal arrhythmogenic disorder that is characterized by prolonged corrected QT (QTc) interval. Mutations in three genes (KCNQ1, KCNH2, and SCN5A) account for the majority of the cases. However, 10 other genes are now known to be implicated in LQTS. In this work, we describe the clinical and molecular analysis in a large Saudi family with LQTS. Screening KCNQ1, KCNH2, and SCN5A genes in the proband, who presented with syncope, led to the identification of a heterozygous mutation (p.H258P) in KCNQ1. An extended clinical and genetic screening of the family identified 11 other members who were carriers for this mutation. All identified carriers had prolonged QTc intervals; yet, only two were symptomatic. Screening the family members for three LQTS modifiers (rs4657139 and rs16847548 in NOS1AP and KCNE1-D85N) did not reveal a correlation with symptoms or QTc intervals. The electrocardiographic and molecular analysis stratified seven carriers at high risk of a cardiac event as they had a QTc of ≥500 ms and were carriers of a KCNQ1 mutation. Our work illustrates the importance of extended family screening in LQTS to identify silent carriers and hence adopt the most appropriate therapeutic and preventive intervention.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | KCNQ1 | “Identification of a novel KCNQ1 mutation in a large Saudi family with long QT syndrome: clinical consequences and preventive implications.” | 0.98 | hgnc_dict_v1 |
| gene | KCNH2 | “Mutations in three genes (KCNQ1, KCNH2, and SCN5A) account for the majority of the cases.” | 0.98 | hgnc_dict_v1 |
| gene | SCN5A | “Mutations in three genes (KCNQ1, KCNH2, and SCN5A) account for the majority of the cases.” | 0.98 | hgnc_dict_v1 |
| gene | NOS1AP | “Screening the family members for three LQTS modifiers (rs4657139 and rs16847548 in NOS1AP and KCNE1-D85N) did not reveal a correlation with symptoms or QTc intervals.” | 0.98 | hgnc_dict_v1 |
| phenotype | long QT syndrome | “Identification of a novel KCNQ1 mutation in a large Saudi family with long QT syndrome: clinical consequences and preventive implications.” | 0.98 | phenotype_alias_lexicon_v2 |
| population | Saudi Arabia | “Identification of a novel KCNQ1 mutation in a large Saudi family with long QT syndrome: clinical consequences and preventive implications. In this work, we describe the clinical and molecular analysis in a large Saudi family with LQTS.” | 0.95 | saudi_context_rules_v1 |
| variant | p.H258P | “Screening KCNQ1, KCNH2, and SCN5A genes in the proband, who presented with syncope, led to the identification of a heterozygous mutation (p.H258P) in KCNQ1.” | 0.95 | hgvs_regex_v1 |
| variant | rs4657139 | “Screening the family members for three LQTS modifiers (rs4657139 and rs16847548 in NOS1AP and KCNE1-D85N) did not reveal a correlation with symptoms or QTc intervals.” | 0.90 | hgvs_regex_v1 |
| variant | rs16847548 | “Screening the family members for three LQTS modifiers (rs4657139 and rs16847548 in NOS1AP and KCNE1-D85N) did not reveal a correlation with symptoms or QTc intervals.” | 0.90 | hgvs_regex_v1 |