A novel nonsense variant in EXOC8 underlies a neurodevelopmental disorder

Ullah, Asmat; Krishin, Jai; Haider, Nighat; Aurangzeb, Brekhna; Abdullah, Abdullah; Suleman, Sufyan; Ahmad, Wasim; Hansen, Torben; Basit, Sulman

doi:10.1007/s10048-022-00692-7

Cited by 5 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is found to play an essential role in normal cortical development and its perturbation causes complex brain disorders. EXOC8 mutations (one family) are linked to neurodevelopmental disorders with microcephaly, seizures, and brain atrophy 63 ?Neurodevelopmental disorder with microcephaly, seizures, and brain atrophy (MIM# 619,076), Two studies correlated EXOC8 variants with a neurodevelopmental phenotype 63 , 64 , functional studies of the variant and studies of patient cells were not performed 10DF16100 14 Years Female Yes Prenatal growth restrictions, failure to thrive, short stature, global developmental delay, intracerebral calcification and basal ganglia calcifications, and kidney failure EXOSC4 EXOSC4(NM_019037.3):c.560 T > C (p.Leu187Pro) homozygous Yes NA Absent 2/4 EXOSC4 is a non-catalytic component of the RNA exosome complex with 3'- > 5' exoribonuclease activity and involvement in numerous cellular RNA processing and degradation events 65 . EXOSC4 is involved in the nucleic acid metabolic process and positive regulation of cell growth 66 .…”

Section: Discussionmentioning

confidence: 99%

The diagnostic yield, candidate genes, and pitfalls for a genetic study of intellectual disability in 118 middle eastern families

Al‐Kasbi

Al-Murshedi

Al-Kindi

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Global Developmental Delay/Intellectual disability (ID) is the term used to describe various disorders caused by abnormal brain development and characterized by impairments in cognition, communication, behavior, or motor skills. In the past few years, whole-exome sequencing (WES) has been proven to be a powerful, robust, and scalable approach for candidate gene discoveries in consanguineous populations. In this study, we recruited 215 patients affected with ID from 118 Middle Eastern families. Whole-exome sequencing was completed for 188 individuals. The average age at which WES was completed was 8.5 years. Pathogenic or likely pathogenic variants were detected in 32/118 families (27%). Variants of uncertain significance were seen in 33/118 families (28%). The candidate genes with a possible association with ID were detected in 32/118 (27%) with a total number of 64 affected individuals. These genes are novel, were previously reported in a single family, or cause strikingly different phenotypes with a different mode of inheritance. These genes included: AATK, AP1G2, CAMSAP1, CCDC9B, CNTROB, DNAH14, DNAJB4, DRG1, DTNBP1, EDRF1, EEF1D, EXOC8, EXOSC4, FARSB, FBXO22, FILIP1, INPP4A, P2RX7, PRDM13, PTRHD1, SCN10A, SCYL2, SMG8, SUPV3L1, TACC2, THUMPD1, XPR1, ZFYVE28. During the 5 years of the study and through gene matching databases, several of these genes have now been confirmed as causative of ID. In conclusion, understanding the causes of ID will help understand biological mechanisms, provide precise counseling for affected families, and aid in primary prevention.

show abstract

Section: Discussionmentioning

confidence: 99%

The diagnostic yield, candidate genes, and pitfalls for a genetic study of intellectual disability in 118 middle eastern families

Al‐Kasbi

Al-Murshedi

Al-Kindi

et al. 2022

Sci Rep

View full text Add to dashboard Cite

show abstract

“…For insights into the effectiveness of eigenvalue-dependent spectral descriptors in E π prediction for BHs, readers are directed to [42,43]. Additionally, recent advancements in QSPR models for chemical/physical characteristics in biomolecular networks as well as nano-structures have been discussed in [44][45][46][47][48]. For the predictive potential of graphical indices for thermodynamic properties of benzenoid hydrocarbons, we refer the reader to [49][50][51][52].…”

Section: Application Of γ In Qspr Modelsmentioning

confidence: 99%

Characterizations of Minimal Dominating Sets in γ-Endowed and Symmetric γ-Endowed Graphs with Applications to Structure-Property Modeling

Hayat,

Sundareswaran,

Shanmugapriya

et al. 2024

Symmetry

View full text Add to dashboard Cite

Claude Berge (1987) introduced the concept of k-extendable graphs, wherein any independent set of size k is inherently a constituent of a maximum independent set within a graph H=(V,E). Graphs possessing the property of being 1-extendable are termedas Berge graphs. This introduction gave rise to the notion of well-covered graphs and well-dominated graphs. A graph is categorized as well-covered if each of its maximal independent sets is, in fact, a maximum independent set. Similarly, a graph attains the classification of well-dominated if every minimal dominating set (DS) within it is a minimum dominating set. In alignment with the concept of k-extendable graphs, the framework of (k,γ)-endowed graphs and symmetric (k,γ)-endowed graphs are established. In these graphs, each DS of size k encompasses a minimum DS of the graph. In this article, a study of γ-endowed dominating sets is initiated. Various results providing a deep insight into γ-endowed dominating sets in graphs such as those characterizing the ones possessing a unique minimum DS are proven. We also introduce and study the symmetric γ-endowed graphs and minimality of dominating sets in them. In addition, we give a solution to an open problem in the literature. which seeks to find a domination-based parameter that has a correlation coefficient of ρ>0.9967 with the total π-electronic energy of lower benzenoid hydrocarbons. We show that the upper dominating number Γ(H) studied in this paper delivers a strong prediction potential.

show abstract

“…Exoc8 can transport intracellular vesicles to the plasma membrane for fusion and plays important roles in several important cellular processes, such as ciliogenesis, cell autophagy, and cytokinesis [55]. Interestingly, some studies have found that exoc8 is closely associated with neural development [56]. A transcriptome analysis of cryopreserved kelp grouper (Epinephelus moara) embryos showed that the expression of some genes encoding proteins that protect neurons from the toxic effects of high concentrations of extracellular neurotransmitters decreased significantly, suggesting that cryopreservation influences the central nervous system of larvae [57].…”

Section: Time-series Expression Profiles and Co-expression Network Of...mentioning

confidence: 99%

Effects of Long-Term Cryopreservation on the Transcriptomes of Giant Grouper Sperm

Ding,

Tian,

Qiu

et al. 2024

Genes

View full text Add to dashboard Cite

The giant grouper fish (Epinephelus lanceolatus), one of the largest and rarest groupers, is a fast-growing economic fish. Grouper sperm is often used for cross-breeding with other fish and therefore sperm cryopreservation is important. However, freezing damage cannot be avoided. Herein, we performed a transcriptome analysis to compare fresh and frozen sperm of the giant grouper with frozen storage times of 0, 23, 49, and 61 months. In total, 1911 differentially expressed genes (DEGs), including 91 in El-0-vs-El-23 (40 upregulated and 51 downregulated), 251 in El-0-vs-El-49 (152 upregulated and 69 downregulated), and 1569 in El-0-vs-El-61 (984 upregulated and 585 downregulated), were obtained in the giant grouper sperm. DEGs were significantly increased at 61 months of cryopreservation (p < 0.05). GO and KEGG enrichment analyses of the DEGs revealed significant enrichment in the pilus assembly, metabolic process, MAPK signaling pathway, apoptosis, and P53 signaling pathway. Time-series expression profiling of the DEGs showed that consistently upregulated modules were also significantly enriched in signaling pathways associated with apoptosis. Four genes, scarb1, odf3, exoc8, and atp5f1d, were associated with mitochondria and flagella in a weighted correlation network analysis. These genes may play an important role in the response to sperm freezing. The experimental results show that long-term cryopreservation results in freezing damage to the giant grouper sperm. This study provides rich data for studies of the mechanism underlying frozen fish sperm damage as well as a technical reference and evaluation index for the long-term cryopreservation of fish sperm.

show abstract

A novel nonsense variant in EXOC8 underlies a neurodevelopmental disorder

Cited by 5 publications

References 19 publications

The diagnostic yield, candidate genes, and pitfalls for a genetic study of intellectual disability in 118 middle eastern families

The diagnostic yield, candidate genes, and pitfalls for a genetic study of intellectual disability in 118 middle eastern families

Characterizations of Minimal Dominating Sets in γ-Endowed and Symmetric γ-Endowed Graphs with Applications to Structure-Property Modeling

Effects of Long-Term Cryopreservation on the Transcriptomes of Giant Grouper Sperm

Contact Info

Product

Resources

About