HNRNPH1 – hnRNP-Related Neurodevelopmental Disorder

HNRNPH1 variants have been implicated in autosomal dominant neurodevelopmental disorder. A male proband presented with dysmorphy, developmental delay, intellectual disability, autism spectrum disorder, hypotonia, and seizures, harboring a de novo heterozygous c.616C>T (p.Arg206Trp) variant in HNRNPH1 (PMID:29938792). A multi-cohort sequencing study of hnRNP family genes identified HNRNPH1 among 12 candidate NDD genes across 119 new cases, supporting its role in cortical development (PMID:33874999). No further familial segregation has been reported.

Direct functional characterization of HNRNPH1 variants in neurodevelopmental contexts is lacking. Expression profiling indicates enriched hnRNP expression in radial glial progenitors, and murine models show genetic compensation of Hnrnph2 by Hnrnph1 (PMID:37463454), suggesting functional overlap. Further in vitro or in vivo studies are needed to define pathogenic mechanisms. Key take-home: De novo HNRNPH1 variants present limited but compelling evidence for autosomal dominant neurodevelopmental disorder; additional work will clarify diagnostic and therapeutic potential.

References

• Clinical genetics • 2018 • Evidence for HNRNPH1 being another gene for Bain type syndromic mental retardation PMID:29938792
• Genome medicine • 2021 • Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders. PMID:33874999
• The Journal of clinical investigation • 2023 • A murine model of hnRNPH2-related neurodevelopmental disorder reveals a mechanism for genetic compensation by Hnrnph1. PMID:37463454

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