Five children with deletions of 1p34.3 encompassing AGO1 and AGO3

Tokita, Mari; Chow, Penny; Mirzaa, Ghayda; Dikow, Nicola; Maas, Bianca; Isidor, Bertrand; Caignec, Cédric Le; Penney, Lynette; Bernardini, Laura; Filippi, Tiziana; Battaglia, Agatino; Donti, Emilio; Earl, Dawn; Prontera, Paolo

doi:10.1038/ejhg.2014.202

Cited by 24 publications

(29 citation statements)

References 20 publications

(35 reference statements)

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“…Recent SFARI study has identified missense mutations in miRISC proteins AGO1, TNRC6B, and CNOT3 among patients diagnosed with Autism Spectrum Disorders (Chen et al, 2019) Patients with microdeletions of chromosomal region 1p34.3 encompassing the AGO1 and AGO3 genes also show several neurodevelopmental defects (Tokita et al, 2015). Similarly, studies have also identified a crucial role of miRISC in neurodegenerative disorders.…”

Section: Discussionmentioning

confidence: 98%

The Role of Dynamic miRISC During Neuronal Development

Nawalpuri

Ravindran

Muddashetty

2020

Front. Mol. Biosci.

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Activity-dependent protein synthesis plays an important role during neuronal development by fine-tuning the formation and function of neuronal circuits. Recent studies have shown that miRNAs are integral to this regulation because of their ability to control protein synthesis in a rapid, specific and potentially reversible manner. miRNA mediated regulation is a multistep process that involves inhibition of translation before degradation of targeted mRNA, which provides the possibility to store and reverse the inhibition at multiple stages. This flexibility is primarily thought to be derived from the composition of miRNA induced silencing complex (miRISC). AGO2 is likely the only obligatory component of miRISC, while multiple RBPs are shown to be associated with this core miRISC to form diverse miRISC complexes. The formation of these heterogeneous miRISC complexes is intricately regulated by various extracellular signals and cell-specific contexts. In this review, we discuss the composition of miRISC and its functions during neuronal development. Neurodevelopment is guided by both internal programs and external cues. Neuronal activity and external signals play an important role in the formation and refining of the neuronal network. miRISC composition and diversity have a critical role at distinct stages of neurodevelopment. Even though there is a good amount of literature available on the role of miRNAs mediated regulation of neuronal development, surprisingly the role of miRISC composition and its functional dynamics in neuronal development is not much discussed. In this article, we review the available literature on the heterogeneity of the neuronal miRISC composition and how this may influence translation regulation in the context of neuronal development.

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Section: Discussionmentioning

confidence: 98%

The Role of Dynamic miRISC During Neuronal Development

Nawalpuri

Ravindran

Muddashetty

2020

Front. Mol. Biosci.

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“…Tokita et al. (), described three individuals whose 1p34.3 deletions also encompass the SNIP1 gene (probands 1, 2, and 4). All three had a history of motor and speech delays of unknown severity; however, as mentioned previously, their deletions also included the AGO1 and AGO3 genes which have been hypothesized to be associated with developmental delays, hypotonia, and poor feeding.…”

Section: Discussionmentioning

confidence: 99%

“…To our knowledge, there have not been individuals reported with the 1p34.3p34.2 deletion reported here, that do not also encompass AGO1, AGO3, GRIK3, SLC2A1, or RIMS3 . All five of these genes have been speculated or proven to be associated with neurocognitive delays (Tokita et al., ; Takenouchi et al., ; Delisi et al., ; Vermeer et al., ; Lee et al., ; Kumar et al., ). Clinical similarities between our patient and those described in the literature include the following: intellectual disability, developmental delay, and kyphoscoliosis.…”

Section: Discussionmentioning

confidence: 99%

“…In the 1p34.3p34.2 region of the genome there have been several genes identified to cause neurodevelopmental delays. The AGO1 (OMIM 606228) and AGO3 (OMIM 607355) genes when deleted have been hypothesized to be associated with developmental delays, hypotonia, and poor feeding (Tokita et al., ). Deletions of the GRIK family genes have been associated with intellectual disability (Takenouchi et al., ).…”

Section: Introductionmentioning

confidence: 99%

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Interstitial microdeletion of the 1p34.3p34.2 region

Jacher

Innis

2018

Molec Gen & Gen Med

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BackgroundInterstitial microdeletions of chromosome 1p34.3p34.2 are rare, but are continuing to be identified by the use of chromosome microarray. There have been fewer than 10 individuals identified who have deletions of the 1p34.3p34.2 region; all of these previously described individuals have deletions of the AGO1, AGO3, GRIK3, SLC2A1, or RIMS3 genes. Haploinsufficiency of these genes has been associated with neurodevelopmental delays.MethodsChromosome microarray, quantitative PCR, and fluorescence in situ hybridization were performed with DNA extracted from peripheral blood.ResultsChromosome microarray identified a 2.3 Mb 1p34.3p34.2 one copy deletion in our patient with global developmental delay, mild intellectual disability, delayed bone age, bilateral vesicoureteral reflux, vocal cord paralysis, right aberrant subclavian artery, kyphoscoliosis, bilateral metatarsus adductus, and valgus knee deformity. This deletion was confirmed by quantitative PCR and does not include the AGO1, AGO3, GRIK3, SLC2A1, or RIMS3 genes. Subsequent FISH testing of the parents was negative.ConclusionHaploinsufficiency of the 1p34.3p34.2 region, including the SNIP1 gene and excluding the five genes listed above, is responsible for the neurocognitive delays and other symptoms as identified in our patient.

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“…Brain magnetic resonance imaging (MRI) was performed on the two living affected members of the family (III–2 and IV–1). Array CGH‐analysis (CytoChip ISCA 4 × 180 K v1.0 BlueGnome, Cambridge, UK) and Fragile‐X genetic tests were performed on both living patients, as described previously [Cavani et al, ; Tokita et al, ].…”

Section: Methodsmentioning

confidence: 99%

A novel MED12 mutation: Evidence for a fourth phenotype

Prontera

Ottaviani

Rogaia

et al. 2016

American J of Med Genetics Pt A

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Mutations of the MED12 gene have been reported mainly in males with FG (Opitz-Kaveggia), Lujan-Fryns, or X-linked Ohdo syndromes. Recently, a different phenotype characterized by minor anomalies, severe intellectual disability (ID), and absent language was reported in female and male patients belonging to the same family and carrying a frameshift MED12 mutation (c.5898dupC). Here, we report on two brothers and their niece affected by severe and mild ID, respectively, where whole exome sequencing combined with variant analysis within a panel of ID-related genes, disclosed a novel c.2312T>C (p.Ile771Thr) MED12 mutation. This variant, which has not been reported as a polymorphism, was not present in a third unaffected brother, and was predicted to be deleterious by five bioinformatic databases. This finding together with the phenotypic analogies shared with the carriers of c.5898dupC mutation suggests the existence of a fourth MED12-related disorder, characterized by severe ID, absent or deficient language and, milder, clinical manifestation in heterozygotes. We have reviewed the literature on MED12 heterozygotes, their clinical manifestations, and discuss the possible biological causes of this condition. © 2016 Wiley Periodicals, Inc.

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Five children with deletions of 1p34.3 encompassing AGO1 and AGO3

Cited by 24 publications

References 20 publications

The Role of Dynamic miRISC During Neuronal Development

The Role of Dynamic miRISC During Neuronal Development

Interstitial microdeletion of the 1p34.3p34.2 region

A novel MED12 mutation: Evidence for a fourth phenotype

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