Carrier frequency of autosomal recessive genetic conditions in diverse populations: Lessons learned from the genome aggregation database.

An equitable approach by the American College of Medical Genetics and Genomics (ACMG) has recently recommended carrier screening for genes associated with moderate to severe autosomal recessive conditions with a carrier frequency of ≥1/200 in the Genome Aggregation Database exomes (gnomADv2.0.2). We analyzed carrier frequencies in gnomADv3.1.1 genomes representing diverse populations. ClinVar data on 35 996 pathogenic/likely pathogenic variants in 419 genes were used to estimate the gnomAD frequency of heterozygous carriers. We found that ninety-two genes had a carrier frequency of ≥1/200, of which 63 were shared between v3.1.1 and v2.0.2 and 29 were new in v3.1.1. Addition of new populations (Amish, Finnish and Middle Eastern) increased the number of new genes with a carrier frequency of ≥1/200 to 71. Changes in carrier frequencies were attributed to new gnomAD populations, different sample sizes, new ClinVar data, and technical differences between exomes and genomes. This study highlights the dynamic changes in carrier frequencies due to new datasets from diverse populations and provides updated carrier frequencies based on the combined data from 184 352 genomes and exomes in gnomAD. We recommend a periodic review for inclusion of new population data to update carrier screening panels in the future.

Ischemic Reperfusion Injury After Liver Transplantation: Is There a Place for Conservative Management?

Ischemic reperfusion injury (IRI) after liver transplantation is a common cause of early allograft dysfunction with high mortality. The purpose of this case report series is to highlight an unusual clinical course in which complete recovery can occur following the identification of severe hepatic IRI post-transplantation and the implications of this finding on management strategies in patients with IRI post-transplant. Here, we include three cases of severe IRI following liver transplantation that are putatively resolved without retransplantation or definitive therapeutic intervention. All patients recovered until their final follow-up visits to our institution and developed no significant complications from their injury throughout the course of patient care by our institution after discharge from the hospital.