A Japanese boy with NAA10-related syndrome and hypertrophic cardiomyopathy

Shishido, Ayumi; Morisada, Naoya; Tominaga, Kazuhiro; Uemura, Hiroyasu; Haruna, Akiko; Hanafusa, Hiroaki; Nozu, Kandai; Iijima, Kazumoto

doi:10.1038/s41439-020-00110-0

Cited by 10 publications

(11 citation statements)

References 12 publications

(18 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…She also has stigmatism in her left eye, along with myopia and possible cortical visual impairment. Individual 54 (a male) with p.Thr152Argfs*6 in NAA10 also has microphthalmia, similarly to a previously published case (Cheng et al 2019), whereas the male in Japan did not have microphthalmia (Shishido et al 2020). Individual 55 has p.Glu181Alafs*67 and does not have microphthalmia, indicating that even frameshift variants toward the C-terminus of NAA10 can have quite variable outcomes.…”

Section: Resultssupporting

confidence: 81%

“…One child (Individual 1) was found to have two novel variants on the same sequencing Most of the NAA10 variants are de novo, with the exception of p.Tyr43Ser in a previously reported family (Casey et al 2015), p.Ile72Thr in two families (one of which, Individual 8, was previously reported (Støve et al 2018;Cheng et al 2019) and Individual 54 with frameshift variant p.Thr152Argfs*6, with this same p.Thr152Argfs*6 variant being reported in two other cases (Shishido et al 2020;Cheng et al 2019).…”

Section: Naa10 and Naa15 Variantsmentioning

confidence: 84%

See 1 more Smart Citation

Expanding the Phenotypic spectrum ofNAA10-related neurodevelopmental syndrome andNAA15-related neurodevelopmental syndrome

Lyon

Vedaie

Besheim

et al. 2022

Preprint

View full text Add to dashboard Cite

NAA10 encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. N-alpha-acetylation is one of the most common co-translational protein modifications in humans and is essential for normal cell function. The auxiliary and regulatory subunits of the NatA complex are NAA15 and Huntington-interacting protein (HYPK), respectively. Through a genotype-first approach with primarily exome sequencing, one clinician identified and interviewed the parents of 56 individuals with NAA10 variants and 19 individuals with NAA15 variants. Clinical features of affected individuals include variable levels of intellectual disability, delayed speech and motor milestones and autism spectrum disorder, which are usually more severe in individuals with NAA10 variants compared to those with NAA15 variants. Additionally, some individuals present with mild craniofacial dysmorphology, congenital cardiac anomalies and seizures. The majority of individuals with NAA10 variants present with visual abnormalities, which often include astigmatism, myopia, strabismus, amblyopia, and/or cortical visual impairment. Further, there are a subset of individuals who have exotropia/esotropia, microphthalmia, blindness, and/or have abnormalities to the optic disc or nerve. In individuals with NAA15 variants, visual abnormalities were present in a small subset with strabismus, amblyopia, astigmatism, and other visual impairment, with many individuals affected by this syndrome wearing eyeglasses. We discovered a female (Individual 23) with the common p.Arg83Cys variant, yet she is the only female published to date who was born with microphthalmia, along with stigmatism in her left eye, myopia and possible cortical visual impairment. We report another male with microphthalmia with a frameshift p.Thr152Argfs*6 variant in NAA10. Vineland-3 functional assessment demonstrates that the overall level of functioning for the probands with NAA15 variants was significantly higher than the probands with NAA10 variants. When the results for NAA10 are separated by sex, inheritance pattern, and variant type, it is clear that the frameshift variants located toward the C-terminal end of NAA10 have much less impact on overall functioning. The females with the p.Arg83Cys missense in NAA10 have a similar level of impairment to the females with other missense changes in NAA10. The overall data are consistent with a phenotypic spectrum for these alleles involving multiple organ systems, including visual development, and as such we suggest that the condition involving NAA10 should be interchangeably referred to as Ogden syndrome and/or NAA10-related neurodevelopmental syndrome, and the condition involving NAA15 should be referred to as NAA15-related neurodevelopmental syndrome.

show abstract

Section: Resultssupporting

confidence: 81%

Section: Naa10 and Naa15 Variantsmentioning

confidence: 84%

Expanding the Phenotypic spectrum ofNAA10-related neurodevelopmental syndrome andNAA15-related neurodevelopmental syndrome

Lyon

Vedaie

Besheim

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Compared to missense variants, alterations in the NAA10 gene which result in a (partial) loss of protein function due to reduced mRNA levels can lead to syndromic microphthalmia/anophthalmia in boys (Esmailpour et al, 2014 ; Johnston et al, 2019 ; Shishido et al, 2020 ). Complete loss‐of‐function of NAA10, however, is thought to be lethal in males (Popp et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Confirmation of Ogden syndrome as an X‐linked recessive fatal disorder due to a recurrent NAA10 variant and review of the literature

Gogoll

Steindl

Joset

et al. 2021

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Ogden syndrome is a rare lethal X-linked recessive disorder caused by a recurrent missense variant (Ser37Pro) in the NAA10 gene, encoding the catalytic subunit of the N-terminal acetyltransferase A complex (NatA). So far eight boys of two different families have been described in the literature, all presenting the distinctive and recognizable phenotype, which includes mostly postnatal growth retardation, global severe developmental delay, characteristic craniofacial features, and structural cardiac anomalies and/or arrhythmias. Here, we report the ninth case of Ogden syndrome with an independent recurrence of the Ser37Pro variant. We were able to follow the clinical course of the affected boy and delineate the evolving phenotype from his birth until his unfortunate death at 7 months. We could confirm the associated phenotype as well as the natural history of this severe disease. By describing new presenting features, we are further expanding the clinical spectrum associated with Ogden syndrome and review other phenotypes associated with NAA10 variants.

show abstract

“…Recently, increasing evidence demonstrated that KCNJ2 [128], TLR4 [129], CYP2D6 [130], TLR2 [129], SNX10 [131], SIRT1 [132], PF4 [133], PCYT2 [134] and LGALS3 [135] were altered expression in atrial fibrillation. Studies had shown that KCNJ2 [136], ARG1 [137], TLR4 [138], IFIH1 [139], FBN2 [140], PDK4 [141], TLR8 [142], PDGFC (platelet derived growth factor C) [143], FNIP1 [144], TLR2 [145], PTPN11 [146], LATS2 [147], GCH1 [148], ARFGEF2 [149], CA2 [150], PTPRC (protein tyrosine phosphatase receptor type C) [151], CCR2 [152], GAB1 [153], VEGFA (vascular endothelial growth factor A) [154], UBR1 [155], PHLPP1 [156], MTM1 [157], FMR1 [158], SIRT1 [159], NOD2 [160], MYOF (myoferlin) [161], OSBPL11 [162], ZBTB11 [121], UTRN (utrophin) [163], ZNF593 [164], CCR7 [165], PRDX2 [166], BIN1 [167], NFIC (nuclear factor I C) [168], TCF4 [169], PPP1R13L [124], NDUFB11 [170], TAX1BP3 [171], TRPM4 [172], NMRAL1 [173], LGALS3 [126] and NAA10 [174] were associated with cardiomyopathy. CD274 [175], CEACAM1 [176], STAT1 [177], ARG1 [178], TLR4 [179], LRRK2 [180], ABCA1 [181], IFIH1 [182], TLR5 [183], PTGS2 [184], CYP2D6 [185], RNF213 [186], C9ORF72 [187], JAK2 [188], TLR8 [189], NOTCH2 [190], PDGFC (platelet derived growth factor C) [191], TLR2 [192], PRKAB2 [193], HDAC9 [194], NCOA4 [195], LATS2 [196], DICER1 […”

Section: Discussionmentioning

confidence: 99%

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

Vastrad¹,

Vastrad²

2023

Preprint

View full text Add to dashboard Cite

Coronary artery disease (CAD) is the most common cardiovascular disorder and the leading cause of heart related deaths in world. Increasing molecular targets have been discovered for CAD and CAD - related complications prognosis and therapy. However, there is still an urgent need to identify novel biomarkers. Therefore, we evaluated biomarkers that might help the diagnosis and treatment of CAD and CAD related complications. We searched next generation sequencing (NGS) dataset (GSE202625) and identified differentially expressed genes (DEGs) by comparing CAD and normal control samples using DESeq2. Gene ontology (GO) and pathway enrichment analyses of the DEGs were performed using the g:Profiler online database. The protein protein interaction (PPI) network was plotted with IMEx interactome and visualized using Cytoscape. Module analysis of the PPI network was done using PEWCC1. MiRNA hub gene regulatory network and TF hub gene regulatory network analysis was performed to identify the hub genes, miRNAs and TFs. Receiver operating characteristic (ROC) curve analysis was used to predict the diagnostic effectiveness of the hub genes. A total of 118 DEGs (479 up regulated genes and 479 down regulated genes) were detected. The GO enrichment analysis indicated that the DEGs most significantly enriched in cellular response to stimulus and biosynthetic process. The REACTOME pathway enrichment analysis revealed that the DEGs were most significantly enriched in immune system and eukaryotic translation elongation. PPI network, modules, miRNA hub gene regulatory network and TF hub gene regulatory network analysis demonstrated that EGR1, SIRT1, STAT1, LRRK2, HIF1A, CSNK2B, RPS3, RPS2, RPS4X and HDAC11 were the hub genes. On the whole, the findings of this study enhance our understanding of the potential molecular mechanisms of CAD and CAD-related complications, and provide potential targets for further research.

show abstract

A Japanese boy with NAA10-related syndrome and hypertrophic cardiomyopathy

Cited by 10 publications

References 12 publications

Expanding the Phenotypic spectrum ofNAA10-related neurodevelopmental syndrome andNAA15-related neurodevelopmental syndrome

Expanding the Phenotypic spectrum ofNAA10-related neurodevelopmental syndrome andNAA15-related neurodevelopmental syndrome

Confirmation of Ogden syndrome as an X‐linked recessive fatal disorder due to a recurrent NAA10 variant and review of the literature

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

Contact Info

Product

Resources

About