RECQL5 – Coronary artery disorder

Two unrelated families with early-onset coronary artery disorder, including myocardial infarction and atherosclerosis, have been reported with rare RECQL5 variants. In a Chinese pedigree, a heterozygous missense change, c.1247T>C (p.Ile416Thr), was identified in the proband, her sister, and their mother, cosegregating with disease and absent in 200 local controls, consistent with autosomal dominant transmission (PMID:37180972). In a second kindred, four siblings with early myocardial infarction were homozygous for a TG insertion at the intron 11 acceptor splice site, leading to exon 12 skipping and trace mRNA levels in homozygotes versus 48–55 % in heterozygotes, supporting an autosomal recessive mechanism (PMID:26844521). Together, seven affected individuals across two families provide limited genetic evidence for RECQL5 in Coronary artery disorder.

Functional data corroborate pathogenicity: the TG insertion abolishes normal splicing by RT-PCR (PMID:26844521), and bioinformatic analyses predict that p.Ile416Thr perturbs a conserved helicase domain, altering hydrophobic surface and protein stability (PMID:37180972). No conflicting reports have been described to date. Additional population and mechanistic studies are needed to strengthen this association. Key take-home: RECQL5 variants may underlie early coronary artery disorder via both dominant missense and recessive splicing defects, informing genetic diagnosis and counseling.

References

• Frontiers in genetics • 2023 • Case report: A novel mutation of RecQ-like helicase 5 in a Chinese family with early myocardial infarction, coronary artery disease, and stroke hemiplegia PMID:37180972
• Medicine • 2016 • Exome Sequencing in a Family Identifies RECQL5 Mutation Resulting in Early Myocardial Infarction PMID:26844521

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