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Fetal anomalies v1.558 RNU4-2 Ee Ming Wong changed review comment from: Monoallelic association - PMID 39830270: Reports 36 individuals from 13 unrelated families with heterozygous dominant variants n.18_19insA and n.56T>C in RNU4-2 presenting with autosomal dominant retinitis pigmentosa (adRP). Night‑blindness and progressive peripheral vision loss start in late adolescence/early adulthood, with classic RP fundus changes, cystoid macular edema, and cataracts. Both inherited and de novo cases are observed. Immunoprecipitation assays demonstrate increased association of mutant U4 snRNA with di‑snRNP proteins SART3 and PRPF31, indicating a gain‑of‑function/dominant‑negative effect on snRNP biogenesis. PREPRINT

Biallelic association - PMID 40297424: preprint reporting 16 individuals from 10 families with balletic variants and presenting with global developmental delay, intellectual disability, speech delay or absence, hypotonia, spasticity, microcephaly, ophthalmologic and visual impairment, seizures, and variable genital, skin, hair and limb anomalies; brain MRI shows distinctive white‑matter abnormalities and cerebellar atrophy.

Disease mechanism not established as yet.
Sources: Literature; to: PMID 39830270: Reports 36 individuals from 13 unrelated families with heterozygous dominant variants n.18_19insA and n.56T>C in RNU4-2 presenting with autosomal dominant retinitis pigmentosa (adRP). Night‑blindness and progressive peripheral vision loss start in late adolescence/early adulthood, with classic RP fundus changes, cystoid macular edema, and cataracts. Both inherited and de novo cases are observed. Immunoprecipitation assays demonstrate increased association of mutant U4 snRNA with di‑snRNP proteins SART3 and PRPF31, indicating a gain‑of‑function/dominant‑negative effect on snRNP biogenesis. PREPRINT

PMID 40297424: preprint reporting 16 individuals from 10 families with balletic variants and presenting with global developmental delay, intellectual disability, speech delay or absence, hypotonia, spasticity, microcephaly, ophthalmologic and visual impairment, seizures, and variable genital, skin, hair and limb anomalies; brain MRI shows distinctive white‑matter abnormalities and cerebellar atrophy.

Disease mechanism not established as yet.
Sources: Literature
Fetal anomalies v1.558 RNU4-2 Ee Ming Wong gene: RNU4-2 was added
gene: RNU4-2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RNU4-2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RNU4-2 were set to 38991538; 40297424; 39830270; 39423747
Phenotypes for gene: RNU4-2 were set to ReNU syndrome (MIM# 620851), AD
Mode of pathogenicity for gene: RNU4-2 was set to Other
Review for gene: RNU4-2 was set to GREEN
gene: RNU4-2 was marked as current diagnostic
Added comment: Monoallelic association - PMID 39830270: Reports 36 individuals from 13 unrelated families with heterozygous dominant variants n.18_19insA and n.56T>C in RNU4-2 presenting with autosomal dominant retinitis pigmentosa (adRP). Night‑blindness and progressive peripheral vision loss start in late adolescence/early adulthood, with classic RP fundus changes, cystoid macular edema, and cataracts. Both inherited and de novo cases are observed. Immunoprecipitation assays demonstrate increased association of mutant U4 snRNA with di‑snRNP proteins SART3 and PRPF31, indicating a gain‑of‑function/dominant‑negative effect on snRNP biogenesis. PREPRINT

Biallelic association - PMID 40297424: preprint reporting 16 individuals from 10 families with balletic variants and presenting with global developmental delay, intellectual disability, speech delay or absence, hypotonia, spasticity, microcephaly, ophthalmologic and visual impairment, seizures, and variable genital, skin, hair and limb anomalies; brain MRI shows distinctive white‑matter abnormalities and cerebellar atrophy.

Disease mechanism not established as yet.
Sources: Literature