Confirmation of the<i>MIR204</i>n.37C&gt;T heterozygous variant as a cause of chorioretinal dystrophy variably associated with iris coloboma, early-onset cataracts and congenital glaucoma

Jedličková, Jana; Vajter, Marie; Bárta, Tomáš; Black, Graeme; Mareš, Jan; Fichtl, Marek; Kousal, Bohdan; Ďuďáková, Ľubica; Lišková, Petra

doi:10.1101/2023.02.09.23284763

Cited by 3 publications

(6 citation statements)

References 22 publications

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“…The pathogenic variant in miR‐204 was first reported in a case of retinal degeneration associated with ocular coloboma, characterized by iris keyhole‐shaped defects, sometimes accompanied by congenital cataract (Conte et al., 2015). In 2023, this pathogenic variant was observed also in a Czech family and associated with congenital glaucoma, besides RP and iris coloboma (Jedlickova et al., 2023). In our patient, WES revealed a miR‐204 n.37C>T variant.…”

Section: Discussionmentioning

confidence: 99%

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Retinitis pigmentosa with iris coloboma due to miR‐204 gene variant in a Chinese family

Lei,

He‐Lin,

Hai‐Yan

et al. 2024

Molec Gen & Gen Med

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PurposeTo characterize the phenotype and genotype of a Chinese family with autosomal‐dominant retinitis pigmentosa (RP) accompanied by iris coloboma.MethodsThe proband, a 34‐year‐old male, was examined with his family by using fundus photography, optical coherence tomography (OCT), autofluorescence, and full‐field electroretinography (ffERG). Genetic analyses were conducted through whole‐exome sequencing (WES) to screen for variations.ResultsThree members of this Chinese family were shown to be bilateral iris coloboma. The male proband and his mother exhibited typical RP feature. The proband's late grandfather had been documented manifestation of iris coloboma. The mode of inheritance was confirmed to be autosomal dominance. Through linkage analysis and WES, a heterozygous variation in the miR‐204 gene (n.37C>T), a noncoding RNA gene, was identified in these three members.ConclusionsIn this third independent and the first Asian family, the existence of a miR‐204 variant associated with RP accompanied by iris coloboma was confirmed. Our findings reinforce the significance of miR‐204 as an important factor influencing visual function in the retina. When phenotypes like RP accompanied by iris coloboma in an autosomal‐dominant pattern, including in Chinese patients, miR‐204 aberrations should be considered.

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Section: Discussionmentioning

confidence: 99%

“…(2011) later identified a variant of miR‐184 linked to keratoconus and early‐onset cataracts. MiR‐204 is the first reported miRNA variant with a causal role in inherited retinal dystrophies in two Caucasian families (Conte et al., 2015; Jedlickova et al., 2023). Other miRNAs have been linked to IBD only in mouse models.…”

Section: Discussionmentioning

confidence: 99%

Retinitis pigmentosa with iris coloboma due to miR‐204 gene variant in a Chinese family

Lei,

He‐Lin,

Hai‐Yan

et al. 2024

Molec Gen & Gen Med

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“…While one of these reports documented adult onset cataracts in mice lacking both miR-204 and miR-211 57 , none of these studies reported congenital cataracts or microphthalmia in mice lacking miR-204 expression, suggesting that embryonic lens development in mice does not require miR-204. Interestingly, a dominant point mutation in miR-204 is associated with several ocular disorders including early-onset cataracts in humans 60 . In contrast to the apparent normal embryonic lens development in mice lacking miR-204 , morpholino-induced knockdown of miR-204 in medaka fish disrupted both lens and retina development by interfering with the regulation of Meis2 11 .…”

Section: Discussionmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted January 30, 2024. ; https://doi.org/10.1101/2024.01.29.577818 doi: bioRxiv preprint several ocular disorders including early-onset cataracts in humans 60 . In contrast to the apparent normal embryonic lens development in mice lacking miR-204, morpholinoinduced knockdown of miR-204 in medaka fish disrupted both lens and retina development by interfering with the regulation of Meis2 11 .…”

Section: Discussionmentioning

confidence: 99%

miR-26 deficiency causes alterations in lens transcriptome and results in adult-onset cataract

Upreti,

Hoang,

et al. 2024

Preprint

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PurposeDespite strong evidence demonstrating that normal lens development requires regulation governed by miRNAs, the functional role of specific miRNAs in mammalian lens development remains largely unexplored.MethodsA comprehensive analysis of miRNA transcripts in the newborn mouse lens, exploring both differential expression between lens epithelial cells and lens fiber cells and overall miRNA abundance was conducted by miRNA-seq. Mouse lenses lacking each of three abundantly expressed lens miRNAs: miR-184, miR-26 and miR-1 were analyzed to explore the role of these miRNAs in lens development.ResultsMice lacking all three copies ofmiR-26(miR-26TKO) developed postnatal cataracts as early as 4-6 weeks of age. RNA-seq analysis of neonatal lenses frommiR-26TKOmice exhibited abnormal reduced expression of a cohort of genes found to be lens-enriched and linked to cataract (e.g. Foxe3,Hsf4,Mip,Tdrd7,and numerous crystallin genes), and abnormal elevated expression of genes related to neural development (Lhx3, Neurod4, Shisa7, Elavl3), inflammation (Ccr1, Tnfrsf12a, Csf2ra), the complement pathway, and epithelial to mesenchymal transition (Tnfrsf1a, Ccl7, Stat3, Cntfr).ConclusionmiR-1, miR-184 and miR-26 are each dispensable for normal embryonic lens development. However, loss of miR-26 causes lens transcriptome changes and drives cataract formation.

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“…Interestingly, a dominant point mutation in miR-204 is associated with several ocular disorders, including early-onset cataracts in humans. 68 In contrast to the apparent normal embryonic lens development in mice lacking miR-204, morpholino-induced knockdown of miR-204 in medaka fish disrupted both lens and retina development by interfering with the regulation of Meis2. 14 Surprisingly, deletion of either of the two abundantly expressed miRNAs (miR-1 and miR-184) had no significant effect on the morphologic embryonic development of the mouse lens.…”

Section: Discussionmentioning

confidence: 99%

miR-26 Deficiency Causes Alterations in Lens Transcriptome and Results in Adult-Onset Cataract

Upreti,

Hoang,

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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Purpose Despite strong evidence demonstrating that normal lens development requires regulation governed by microRNAs (miRNAs), the functional role of specific miRNAs in mammalian lens development remains largely unexplored. Methods A comprehensive analysis of miRNA transcripts in the newborn mouse lens, exploring both differential expression between lens epithelial cells and lens fiber cells and overall miRNA abundance, was conducted by miRNA sequencing. Mouse lenses lacking each of three abundantly expressed lens miRNAs (miR-184, miR-26, and miR-1) were analyzed to explore the role of these miRNAs in lens development. Results Mice lacking all three copies of miR-26 ( miR-26 TKO ) developed postnatal cataracts as early as 4 to 6 weeks of age. RNA sequencing analysis of neonatal lenses from miR-26 TKO mice exhibited abnormal reduced expression of a cohort of genes found to be lens enriched and linked to cataract (e.g., Foxe3 , Hsf4 , Mip , Tdrd7 , and numerous crystallin genes) and abnormal elevated expression of genes related to neural development ( Lhx3 , Neurod4 , Shisa7 , Elavl3 ), inflammation ( Ccr1 , Tnfrsf12a , Csf2ra) , the complement pathway, and epithelial to mesenchymal transition ( Tnfrsf1a , Ccl7 , Stat3 , Cntfr ). Conclusions miR-1, miR-184, and miR-26 are each dispensable for normal embryonic lens development. However, loss of miR-26 causes lens transcriptome changes and drives cataract formation.

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Confirmation of theMIR204n.37C>T heterozygous variant as a cause of chorioretinal dystrophy variably associated with iris coloboma, early-onset cataracts and congenital glaucoma

Cited by 3 publications

References 22 publications

Retinitis pigmentosa with iris coloboma due to miR‐204 gene variant in a Chinese family

Retinitis pigmentosa with iris coloboma due to miR‐204 gene variant in a Chinese family

miR-26 deficiency causes alterations in lens transcriptome and results in adult-onset cataract

miR-26 Deficiency Causes Alterations in Lens Transcriptome and Results in Adult-Onset Cataract

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