Ingo Helbig

@IngoHelbig

Child Neurologist, epilepsy genetics researcher, blogger

Philadelphia, USA helbiglab.io Joined March 2009

378 Following 2.5K Followers 2.3K Posts

Latest posts 5

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Ingo Helbig @IngoHelbig May 29, 2025

I became a US citizen today.

...here is my blog post on Life, Liberty, and the Pursuit of Precision Medicine

epilepsygenetics.net/2025/05/29/lif…

Figure 1. Introducing Citizen Helbig. I was naturalized as a United States citizen in Philadelphia today, alongside fellow new citizens from 25 countries, ranging from Afghanistan to Uganda. Also, I was wearing my STXBP1 sock for my naturalization ceremony.

Ingo Helbig @IngoHelbig May 13

After the Genome Comes Time | Beyond the Ion Channel
...I just published a short reflection on today’s Kids First Spring Public Webinar and why the next wave of pediatric genomics will move from genomes to phenomes to time.

epilepsygenetics.blog/2026/05/13/aft…

Ingo Helbig @IngoHelbig May 10

The Spliceosome Strikes Again | Beyond the Ion Channel

...I just published a blog post on three new Nature Genetics papers that place RNU2-2 at the center of recessive developmental and epileptic encephalopathies.

epilepsygenetics.blog/2026/05/10/the…

Figure. Bi-allelic RNU2-2 variants define a developmental and epileptic encephalopathy. Adapted from Jackson et al., 2026 under the Creative Commons Attribution 4.0 International License. Panel A shows that individuals with candidate bi-allelic RNU2-2 variants are more phenotypically similar to each other than expected from random groups of individuals with neurodevelopmental disorders in the 100,000 Genomes Project. Panel B shows the HPO enrichment analysis that defines the clinical signal. Panel C shows the proposed secondary structure of U2-2 in complex with U6, the 5′ splice site, and the splicing branchpoint, based on the four-helix U2/U6 structure. The original article is open access and licensed under CC BY 4.0, which permits use, sharing, adaptation, distribution, and reproduction with appropriate credit to the authors and source, a link to the license, and indication of changes.

Ingo Helbig @IngoHelbig May 7

The Hidden Genome of Treatment | Beyond the Ion Channel
...we just published on why treatment genetics may differ from disease genetics, focusing on the recent GLP1R study in Nature.

...here are the lessons for epilepsy 🔬🧬

epilepsygenetics.blog/2026/05/06/the…

Figure. In the study by Su et al. in Nature of nearly 28,000 individuals treated with GLP-1 receptor agonists, a genome-wide association study identified a common variant in GLP1R (rs10305420) associated with greater weight loss. The Manhattan plot (top) shows a clear genome-wide signal centered on GLP1R, the direct molecular target of semaglutide and tirzepatide. The forest plot (bottom) demonstrates that the effect is directionally consistent across ancestral groups, with the strongest signal in European participants and a significant fixed-effect meta-analysis across cohorts. Importantly, this variant is not primarily associated with obesity risk itself. Instead, it predicts response to treatment, illustrating a central concept in pharmacogenomics: the genetics of drug response may be distinct from the genetics of disease. This distinction is the starting point for understanding why pharmacogenomics in epilepsy remains so difficult.

Ingo Helbig @IngoHelbig Apr 27

STRIPE | Beyond the Ion Channel
...we just published on why rare disease genetics may be shifting from DNA to RNA.

STRIPE uses targeted long-read RNA sequencing to reveal variants missed by standard testing.

epilepsygenetics.blog/2026/04/27/str…

#EpilepsyGenetics #RareDisease

Figure. Transcript-level diagnosis in NGLY1-related disease using STRIPE. In one of the most instructive examples from our publication by Wang et al., STRIPE resolved the transcript consequences of two variants in an individual with NGLY1 deficiency. A maternally inherited frameshift variant and a paternally inherited deep intronic variant converged on a shared transcript-level mechanism: skipping of exon 11. The sashimi plots and isoform analyses show how the paternal allele shifts transcript architecture toward an exon-skipped isoform, a pattern that was largely absent in controls. Long-read sequencing made it possible to phase these changes by parental haplotype and to directly quantify the altered isoform proportions. Genomic long-read sequencing then identified the causative intronic variant, and minigene assays confirmed its effect on splicing.