Variants in HNRNPH2 on the X Chromosome Are Associated with a Neurodevelopmental Disorder in Females

Jennifer M. Bain, Megan T. Cho, Aida Telegrafi, Ashley Wilson, Susan Brooks, Christina Botti, Gordon Gowans, Leigh Anne Autullo, Vidya Krishnamurthy, Marcia C. Willing, Tomi L. Toler, Bruria Ben-Zev, Orly Elpeleg, Yufeng Shen, Kyle Retterer, Kristin G. Monaghan, Wendy K. Chung

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Via whole-exome sequencing, we identified six females from independent families with a common neurodevelopmental phenotype including developmental delay, intellectual disability, autism, hypotonia, and seizures, all with de novo predicted deleterious variants in the nuclear localization signal of Heterogeneous Nuclear Ribonucleoprotein H2, encoded by HNRNPH2, a gene located on the X chromosome. Many of the females also have seizures, psychiatric co-morbidities, and orthopedic, gastrointestinal, and growth problems as well as common dysmorphic facial features. HNRNPs are a large group of ubiquitous proteins that associate with pre-mRNAs in eukaryotic cells to produce a multitude of alternatively spliced mRNA products during development and play an important role in controlling gene expression. The failure to identify affected males, the severity of the neurodevelopmental phenotype in females, and the essential role of this gene suggests that male conceptuses with these variants may not be viable.

Original languageEnglish
Pages (from-to)728-734
Number of pages7
JournalAmerican journal of human genetics
Issue number3
StatePublished - Sep 1 2016


  • X chromosome
  • alternative splicing
  • autism
  • developmental delay
  • microcephaly
  • neurodevelopment
  • pre-mRNA


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