A case report of a novel HIST1H1E mutation and a review of the bibliography to evaluate the genotype–phenotype correlations

Abstract

BackgroundHIST1H1E is a member of the H1 gene family. Excess de novo likely gene‐disruptive variants involving the C‐terminal tail of HIST1H1E have been reported in neurodevelopmental disorders. Although clinical phenotypes in some patients have been described in single studies, few studies have reviewed the genotype and phenotype relationships using a relatively large cohort of patients with HIST1H1E variants.MethodsWhole‐exome sequencing (WES) was performed on the proband. The variant was validated using Sanger sequencing in both proband and parents. Published HIST1H1E variants in neuropsychiatric disorders were reviewed.ResultsHerein, we reported a new de novo frameshift mutation in HIST1H1E (NM_005321.2, c.416_419dupAGAA, p.Ala141GlufsTer56) in an individual with Rahman syndrome. To explore the genotype–phenotype correlations for HIST1H1E variants in neurodevelopmental disorders, we comprehensively curated and summarized 23 variants and the clinical features from 52 patients. Our findings revealed that likely gene‐disrupting variants in HIST1H1E contribute to a wide range of neurodevelopmental phenotypes. We observed the common phenotypes including craniofacial features, ID, hypotonia, and autism/behavior problem in patients with HIST1H1E variants. While the different genotypes corresponding to different phenotypes or the same phenotype were also observed.ConclusionThese data provide scientific evidence for the genetic diagnosis and precision clinical management.

Differential proteomics of circulating extracellular vesicles of placental origin isolated from women with early‐onset preeclampsia reveal aberrant innate immune and hemostasis processes

“…Aldolase A, a sensor of glucose availability is known to be overexpressed in cancer and is associated with poor prognosis and reduced survival 86 . Histone H1.4 variants are frequently found in neurodevelopmental disorders that range from mild to severe intellectual disability 87 . Preeclampsia is associated with elevated levels of an isoform of carbonic anhydrase, CA‐IX, a marker of hypoxia, in the maternal circulation of EOPE women before the clinical manifestation 88 …”

“…86 Histone H1.4 variants are frequently found in neurodevelopmental disorders that range from mild to severe intellectual disability. 87 Preeclampsia is associated with elevated levels of an isoform of carbonic anhydrase, CA-IX, a marker of hypoxia, in the maternal circulation of EOPE women before the clinical manifestation. 88 It is also worth noting that 19 of the 26 differential proteins (Table S2) were implicated in the pathogenesis of EOPE, confirming the hypothesis that dysregulated content found in the placental EVs is directly involved in placental pathologies 89,90 including EOPE.…”