Fanconi anemia is a rare and aggressive genetic disorder that affects bone marrow function and increases cancer risk. Despite advances in treatment, many individuals with this condition do not survive into adulthood without bone marrow transplantation and regular cancer screening. However, a recent study has identified a new gene, FANCX, which plays a critical role in the Fanconi anemia pathway. This discovery sheds light on the severity of Fanconi anemia caused by mutations in FANCX.

Researchers from Rockefeller University’s Laboratory of Genome Maintenance, led by Agata Smogorzewska, have been studying the Fanconi anemia pathway and its associated genes for years. They discovered that FANCX is a previously unknown gene involved in this pathway, and its mutations result in a more severe form of Fanconi anemia.

The researchers began to suspect that Fanconi anemia patients hadn’t presented with FANCX mutations until now because these mutations are so severe. Without the protein produced by FANCX, it’s unlikely that a fetus will survive. Smogorzewska and her team started looking for FANCX mutations in families with multiple miscarriages, which led to the identification of several cases.

The findings of this study have significant implications for families affected by Fanconi anemia. With the help of Kasturba Medical College in India, the researchers identified a second family with two miscarriages, and studies revealed that the mutant protein from that family lacked normal function. This discovery may soon enable clinicians to screen for FANCX mutations during IVF, selecting only healthy embryos for implantation.

The study’s lead author, Agata Smogorzewska, emphasizes the importance of collaboration in rare disease research. She highlights the role of the Fanconi Cancer Foundation in facilitating research and coordinating publications with other researchers. The foundation makes a significant contribution to the advancement of knowledge in this area, allowing families, patients, clinicians, and researchers to collaborate and compete.

The discovery of FANCX as a new Fanconi anemia gene has far-reaching implications for our understanding of this condition and its management. It may soon be possible to help families that carry these mutations prevent Fanconi anemia in future pregnancies by screening for FANCX mutations during IVF. The researchers now know what they’re looking for, which brings hope to those affected by this rare and aggressive genetic disorder.

The world of newborn genetic screening has come a long way since the launch of the BabySeq Project over a decade ago. Today, more than 30 international initiatives are exploring the expansion of this critical public health tool using genomic sequencing (NBSeq). However, a recent study by researchers from Mass General Brigham highlights the substantial variability in gene selection among these programs. In a paper published in Genetics in Medicine, the researchers offer a data-driven approach to prioritizing genes for public health consideration.

“It’s essential that we be thoughtful about which genes and conditions are included in genomic newborn screening programs,” said co-senior author Nina Gold, MD, director of Prenatal Medical Genetics and Metabolism at Massachusetts General Hospital (MGH), a founding member of the Mass General Brigham healthcare system. “By leveraging machine learning, we can provide a tool that helps policymakers and clinicians make more informed choices, ultimately improving the impact of genomic screening programs.”

The researchers introduced a machine learning model that brings structure and consistency to the selection of genes for NBSeq programs. This is the first publication from the International Consortium of Newborn Sequencing (ICoNS), founded in 2021 by senior author Robert C. Green, MD, MPH, director of the Genomes2People Research Program at Mass General Brigham, and David Bick, MD, PhD, of Genomics England in the United Kingdom.

The study analyzed 4,390 genes included across 27 NBSeq programs, identifying key factors influencing gene inclusion. While the number of genes analyzed by each program ranged from 134 to 4,299, only 74 genes (1.7%) were consistently included in over 80% of programs. The strongest predictors of gene inclusion were whether the condition is on the U.S. Recommended Uniform Screening Panel, has robust natural history data, and if there is strong evidence of treatment efficacy.

Using these insights, the team developed a machine learning model incorporating 13 predictors, achieving high accuracy in predicting gene selection across programs. The model provides a ranked list of genes that can adapt to new evidence and regional needs, enabling more consistent and informed decision-making in NBSeq initiatives worldwide.

“This research represents a significant step toward harmonizing NBSeq programs and ensuring that gene selection reflects the latest scientific evidence and public health priorities,” said Green.

The story begins with a simple yet fascinating connection between modern HIV medicine and an ancient human from the Black Sea region. Researchers at the University of Copenhagen have now unraveled the mystery behind a millennia-old genetic mutation that protects against HIV, affecting 18-25% of the Danish population. This breakthrough has shed light on the origins of this crucial genetic variation.

The researchers employed advanced DNA technology to analyze the genetic material of over 2,000 living people worldwide and developed an AI-based method to identify the mutation in ancient DNA from old bones. By examining data from over 900 skeletons dating from the early Stone Age to the Viking Age, they pinpointed the region where the mutation originated – a person from the Black Sea region up to 9,000 years ago.

But why did this genetic mutation arise and spread rapidly among our ancestors? The researchers believe it provided an advantage in surviving during a time when humans were exposed to new pathogens. This variation disrupted an immune gene, which may have been beneficial by dampening the immune system. As humans transitioned from hunter-gatherers to living closely together in agricultural societies, the pressure from infectious diseases increased, and a more balanced immune system may have been advantageous.

The discovery of this 7,000-year-old genetic mutation not only reveals ancient secrets but also provides valuable insights into modern HIV medicine. It highlights the importance of understanding our evolutionary history and how it has shaped our genetic makeup. This breakthrough opens up new avenues for research, potentially leading to innovative treatments for various diseases.