Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Variants in HNRNPH2 on the X Chromosome Are Associated with a Neurodevelopmental Disorder in Females. 2754 75

The HNRNPH2-associated disease (mental retardation, X-linked, syndromic, Bain type [MRXSB, MIM #300986]) is caused by de novo mutations in the X-linked HNRNPH2 gene. MRXSB has been described in six female patients with dysmorphy, developmental delay, intellectual disability, autism, hypotonia and seizures. The reported HNRNPH2 mutations were clustered in the small domain encoding nuclear localization signal; in particular, the p.Arg206Trp was found in four independent de novo events. HNRNPH1 is a conserved autosomal paralogue of HNRNPH2 with a similar function in regulation of pre-mRNAs splicing but so far it has not been associated with human disease. We describe a boy with a disease similar to MRXSB in whom a novel de novo mutation c.616C>T (p.Arg206Trp) in HNRNPH1 was found (ie, the exact paralogue of the recurrent HNRNPH2 mutation). We propose that defective function of HNRNPH2 and HNRNPH1 nuclear localization signal has similar clinical consequences. An important difference between the two diseases is that the HNRNPH1-associated syndrome may occur in boys (as in the case of our proband) which is well explained by the autosomal (chr5q35.3) rather than X-linked localization of the HNRNPH2 gene.
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PMID:Evidence for HNRNPH1 being another gene for Bain type syndromic mental retardation. 3088 13

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA binding proteins, which aid in maturation, stabilization, and transport of mRNA. They have a significant role in cellular nucleic acid metabolism. The hnRNPs alter gene expression and are linked to various neurodegenerative disorders and cancers. Previously, six unrelated girls with developmental delay, intellectual disability, and hypotonia were found to have de novo heterozygous pathogenic missense variants in HNRNPH2, located on the X chromosome. A gain-of-function effect was proposed for the variant and it was thought to be lethal in males as no surviving males were identified. We describe a family with two affected siblings, one male and one female, with a known pathogenic variant in HNRNPH2, possibly due to maternal germline mosaicism.
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PMID:Bain type of X-linked syndromic mental retardation in a male with a pathogenic variant in HNRNPH2. 3167 Apr 73