NDUFV1 mutations in complex I deficiency: Case reports and review of symptoms

Zanette, Vanessa; Valle, Daniel do; Telles, Bruno Augusto; Robinson, Alan J.; Monteiro, Vaneisse Cristina Lima; Santos, Mara Lúcia Schmitz Ferreira; Souza, Ricardo Lehtonen Rodrigues de; Benincá, Cristiane

doi:10.1590/1678-4685-gmb-2021-0149

Cited by 7 publications

(4 citation statements)

References 32 publications

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“…The PC and NDUFV1 are genes present at 11q13.2, which have been associated with pyruvate carboxylase deficiency syndrome (PCDS; OMIM #266150) and mitochondrial complex I deficiency nuclear type 4 (MC1DN4; OMIM #618225), respectively. Both syndromes are associated with loss of function mutations, which promote a mitochondrial metabolism dysfunction [Mhanni et al, 2021;Zanette et al, 2021]. We detected the overexpression of PC and NDUFV1 in different tissues of our patient, who disclosed some overlapping clinical features with PCDS and MC1DN4 including intellectual disability, developmental delay, and corpus callosum dysgenesis (Table 1; Fig.…”

Section: Discussionmentioning

confidence: 73%

Pure Interstitial Trisomy 11q Arising from a Nonrecurrent 11q13.1q22.3 Mosaic Intrachromosomal Duplication in a Patient with Craniofacial Dysmorphism and Genital Anomalies

Anaya¹,

Juárez-Velázquez²,

Ruvalcaba³

et al. 2023

Mol Syndromol

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Introduction: The pure interstitial trisomy 11q11q23.2 is an uncommon genomic disorder associated with nonrecurrent intrachromosomal duplications. The phenotype is characterized by intellectual disability and craniofacial abnormalities. Given their uncommonness, a comprehensive genotype-phenotype correlation has not fully been defined. Case Presentation: We report the clinical and cytogenomic characterization of a 5-year-old boy with intellectual disability, psychomotor retardation, craniofacial dysmorphism, genital anomalies, and pure interstitial trisomy 11q arising from a nonrecurrent 11q13.1q22.3 intrachromosomal duplication in a high-mosaic state (>80%). The duplicated chromosome was characterized by cytogenetics, multicolor banding FISH, and SNP array. We demonstrated the wide mosaic distribution of the 11q duplication by interphase FISH in tissues from different embryonic germ layers. The duplication involves a copy number gain of 45.3 Mb containing 22 dosage-sensitive genes. We confirmed the overexpression of dosage-sensitive genes along the duplicated region using RT-qPCR. Discussion: Only 8 patients have been described. Our patient shares clinical features with previous reports but differs from them by the presence of genital anomalies. We provide a detailed clinical review and an accurate genotype-phenotype correlation and propose PC, NDUFV1, FGF3, FGF4, and DHCR7 as dosage-sensitive genes with a possible role in the clinical spectrum of our patient; however, expression changes of FGF3/4 were not detected since they must be regulated in a spatiotemporal way. This patient contributes to the accurate description of the pure interstitial trisomy 11q. Future reports could continue to delineate the description, considering the relationship between the chromosome segment and the genes involved.

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Section: Discussionmentioning

confidence: 73%

Pure Interstitial Trisomy 11q Arising from a Nonrecurrent 11q13.1q22.3 Mosaic Intrachromosomal Duplication in a Patient with Craniofacial Dysmorphism and Genital Anomalies

Anaya¹,

Juárez-Velázquez²,

Ruvalcaba³

et al. 2023

Mol Syndromol

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“…The brain tissue models are prevalent with three TFs, ETS Proto-Oncogene 1, Transcription Factor (ETS1), Forkhead box protein O1 (FOXO1) and PR/SET Domain 14 (PRDM14), each appearing in almost half of the brain tissues. These TFs are also associated with some of the same neurological conditions associated with regulation of their modeled hit gene, NDUFV1: ETS1 is associated with complex I deficiency [ 42 , 46 ], expression levels of FOXO1 are decreased in acute schizophrenia [ 47 ] and increased in AD [ 48 ]. Finally, PRDM14 has key role in modulating specific regulatory functions in schizophrenia [ 49 ], suggesting a possible mechanism for these three TFs to affect these conditions through NDUFV1.…”

Section: Resultsmentioning

confidence: 99%

Tissue-specific atlas of trans-models for gene regulation elucidates complex regulation patterns

Dagostino,

Gottlieb

2024

BMC Genomics

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Background Deciphering gene regulation is essential for understanding the underlying mechanisms of healthy and disease states. While the regulatory networks formed by transcription factors (TFs) and their target genes has been mostly studied with relation to cis effects such as in TF binding sites, we focused on trans effects of TFs on the expression of their transcribed genes and their potential mechanisms. Results We provide a comprehensive tissue-specific atlas, spanning 49 tissues of TF variations affecting gene expression through computational models considering two potential mechanisms, including combinatorial regulation by the expression of the TFs, and by genetic variants within the TF. We demonstrate that similarity between tissues based on our discovered genes corresponds to other types of tissue similarity. The genes affected by complex TF regulation, and their modelled TFs, were highly enriched for pharmacogenomic functions, while the TFs themselves were also enriched in several cancer and metabolic pathways. Additionally, genes that appear in multiple clusters are enriched for regulation of immune system while tissue clusters include cluster-specific genes that are enriched for biological functions and diseases previously associated with the tissues forming the cluster. Finally, our atlas exposes multilevel regulation across multiple tissues, where TFs regulate other TFs through the two tested mechanisms. Conclusions Our tissue-specific atlas provides hierarchical tissue-specific trans genetic regulations that can be further studied for association with human phenotypes.

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“…8), and is important for supporting overall respiration and mitochondrial integrity (Fig. 4), could implicate CISD3 in some of the different conditions described above, associated with NDUFV2 deficiency, as well as in additional mitochondrial complex I deficiencies, such as fatal neonatal lactic acidosis, leukoencephalopathy, hepatopathy, cardiomyopathy, childhood-onset mitochondrial encephalomyopathy, and stroke-like episodes [54][55][56] . The potential involvement of CISD3 in these and other presentations associated with mitochondrial/Complex I function should be explored in future studies, as CISD3 could become a molecular marker for some of these conditions.…”

Section: Discussionmentioning

confidence: 99%

CISD3 is required for Complex I function, mitochondrial integrity, and skeletal muscle maintenance

Marjault

Rowland

Nguyen

et al. 2023

Preprint

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Mitochondria play a central role in muscle metabolism and function. In skeletal muscles, a unique family of iron-sulfur proteins, termed CISD proteins, support mitochondrial function. The abundance of these proteins declines with aging leading to muscle degeneration. Although the function of the outer mitochondrial proteins CISD1 and CISD2 has been defined, the role of the inner mitochondrial protein CISD3, is currently unknown. Here we show that CISD3 deficiency in mice results in muscle atrophy that shares proteomic features with Duchenne Muscular Dystrophy. We further reveal that CISD3 deficiency impairs the function and structure of skeletal muscle mitochondria, and that CISD3 interacts with, and donates its clusters to, Complex I respiratory chain subunit NDUFV2. These findings reveal that CISD3 is important for supporting the biogenesis and function of Complex I, essential for muscle maintenance and function. Interventions that target CISD3 could therefore impact muscle degeneration syndromes, aging, and related conditions.

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NDUFV1 mutations in complex I deficiency: Case reports and review of symptoms

Cited by 7 publications

References 32 publications

Pure Interstitial Trisomy 11q Arising from a Nonrecurrent 11q13.1q22.3 Mosaic Intrachromosomal Duplication in a Patient with Craniofacial Dysmorphism and Genital Anomalies

Pure Interstitial Trisomy 11q Arising from a Nonrecurrent 11q13.1q22.3 Mosaic Intrachromosomal Duplication in a Patient with Craniofacial Dysmorphism and Genital Anomalies

Tissue-specific atlas of trans-models for gene regulation elucidates complex regulation patterns

CISD3 is required for Complex I function, mitochondrial integrity, and skeletal muscle maintenance

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