Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2025 Jan-Dec;65(1):e70006.
doi: 10.1111/cga.70006.

Severe pharyngeal stenosis and laryngomalacia in an individual of HNRNPU-related neurodevelopmental disorder associated with a novel nonsense variant

Yusuke Sasaki  1 , Hiroaki Murakami  1   2 , Yukiko Kuroda  3 , Yumi Enomoto  4 , Takuya Naruto  4 , Syunsuke Nagara  5 , Toshinari Koyama  6 , Kunihiro Matsunami  1 , Tatsuya Sakashita  1   2 , Hideo Kaneko  2 , Kyoko Morimoto  7 , Atsushi Imamura  1 , Kenji Kurosawa  3   4
Affiliations
Case Reports

Severe pharyngeal stenosis and laryngomalacia in an individual of HNRNPU-related neurodevelopmental disorder associated with a novel nonsense variant

Yusuke Sasaki et al. Congenit Anom (Kyoto). 2025 Jan-Dec.

Abstract

Heterozygous loss-of-function variants in heterogeneous nuclear ribonucleoprotein U (HNRNPU) cause early-onset developmental and epileptic encephalopathy with multiple congenital anomalies. Limited clinical information is currently available on HNRNPU-related neurodevelopmental disorder. The patient was a 1-year-old Japanese girl with developmental delay, hypotonia, early-onset epilepsy, respiratory distress, and distinctive facial features, including ptosis, epicanthus, a prominent nasal bridge, a wide nasal floor, a cleft soft palate, and micrognathia. Respiratory distress was caused by pharyngeal stenosis and laryngomalacia, which gradually worsened, necessitating a scheduled tracheostomy at 1 year and 7 months of age. We performed whole-exome sequencing and identified a novel de novo nonsense variant in HNRNPU. We herein describe the first case of HNRNPU-related neurodevelopmental disorder with severe airway anomalies and a novel nonsense variant, thereby expanding the phenotypic spectrum.

Keywords: HNRNPU; HNRNPU‐related neurodevelopmental disorder; laryngomalacia; pharyngeal stenosis; whole‐exome sequencing.

PubMed Disclaimer

References

REFERENCES

    1. Hasegawa Y, Brockdorff N, Kawano S, Tsutui K, Tsutui K, Nakagawa S. The matrix protein hnRNP U is required for chromosomal localization of Xist RNA. Dev Cell. 2010;19(3):469‐476.
    1. Nozawa R‐S, Boteva L, Soares DC, et al. SAF‐A regulates interphase chromosome structure through oligomerization with chromatin‐associated RNAs. Cell. 2017;169(7):1214‐1227.
    1. Bi H‐s, Yang X‐y, Yuan J‐h, et al. H19 inhibits RNA polymerase II‐mediated transcription by disrupting the hnRNP U‐actin complex. Biochim Biophys Acta. 2013;1830(10):4899‐4906.
    1. Thierry G, Bénéteau C, Pichon O, et al. Molecular characterization of 1q44 microdeletion in 11 patients reveals three candidate genes for intellectual disability and seizures. Am J Med Genet A. 2012;158(7):1633‐1640.
    1. Balasubramanian M, Adam MP, Feldman J, et al. HNRNPU‐Related Neurodevelopmental Disorder, GeneReviews®. 2022. Accessed November 11, 2024. https://www.ncbi.nlm.nih.gov/books/NBK578573/

Publication types

Substances

LinkOut - more resources