Posts in Publications
Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease

Today marks the publication of our manuscript, Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease,” in the New England Journal of Medicine. This article describes an example of individualized genomic medicine: the timely development of a novel drug for a patient with a rare, progressive, neurodegenerative disease. It is accompanied by an editorial penned by Drs. Janet Woodcock and Peter Marks, heads of the FDA’s Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER), respectively.

Congratulations to co-first authors Chungaung “April” Hu, MD, PhD and Jinkuk Kim, PhD! And thank you to an incredible team of collaborators, without whom this work would have never come to fruition: the BCH Departments of Neurology, Anesthesiology, and Genetics, the Institutional Center for Clinical Translational Research at Boston Children’s, the Mazzulli Lab at Northwestern, TriLink, Brammer Bio, Charles River Laboratories, the FDA, and Mila’s Miracle Foundation.

Press Coverage

Recessive Gene Disruptions in Autism

The data in our latest publication in Nature Genetics refine estimates of the contribution of recessive mutations to ASD and suggest new paths for illuminating previously unknown biological pathways responsible for this condition.

Autism spectrum disorder (ASD) affects up to 1 in 59 individuals. Genome-wide association and large-scale sequencing studies strongly implicate both common variants and rare de novo variants in ASD. Recessive mutations have also been implicated but their contribution remains less well defined. Here we demonstrate an excess of biallelic loss-of-function and damaging missense mutations in a large ASD cohort, corresponding to approximately 5% of total cases, including 10% of females, consistent with a female protective effect. We document biallelic disruption of known or emerging recessive neurodevelopmental genes as well as other genes not previously implicated in ASD including FEV (FEV transcription factor, ETS family member), which encodes a key regulator of the serotonergic circuitry.


Press Coverage