Search

Objective: Genetic variants in EFTUD2 were proven to influence variable phenotypic expressivity in mandibulofacial dysostosis Guion-Almeida type (MFDGA) or mandibulofacial dysostosis with microcephaly (MFDM). Yet, the association between the severity of clinical findings with variants within the EFTUD2 gene has not been established. Thus, we aim to elucidate a possible genotype–phenotype correlation in MFDM. Methods: Forty articles comprising 156 patients were evaluated. The genotype–phenotype correlation was analyzed using a chi-square or Fisher's exact test. Results: The proportion of patients with MFDM was higher in Caucasian relative to Asian populations. Although, in general, there was no apparent genotype–phenotype correlation in patients with MFDM, Asians tended to have more severe clinical manifestations than Caucasians. In addition, cardiac abnormality presented in patients with intronic variants located in canonical splice sites was a predisposing factor in affecting MFDM severity. Conclusion: Altogether, this article provides the pathogenic variants observed in EFTUD2 and possible genotype–phenotype relationships in this disease. [ABSTRACT FROM AUTHOR]

Perfluorohexanesulfonic acid (PFHxS) is a highly prevalent environmental pollutant, often considered to be less toxic than other poly- and perfluoroalkyl substances (PFASs). Despite its relatively lower environmental impact compared to other PFASs, several studies have suggested that exposure to PFHxS may be associated with disruptions of liver function in humans. Nevertheless, the precise pathomechanisms underlying PFHxS-induced non-alcoholic fatty liver disease (NAFLD) remain relatively unclear. Therefore, this study applied our previously published transcriptome dataset to explore the effects of PFHxS exposure on the susceptibility to NAFLD and to identify potential mechanisms responsible for PFHxS-induced NAFLD through transcriptomic analysis conducted on zebrafish embryos. Results showed that exposure to PFHxS markedly aggravated hepatic symptoms resembling NAFLD and other metabolic syndromes (MetS) in fish. Transcriptomic analysis unveiled 17 genes consistently observed in both NAFLD and insulin resistance (IR), along with an additional 28 genes identified in both the adipocytokine signaling pathway and IR. These shared genes were also found within the NAFLD dataset, suggesting that hepatic IR may play a prominent role in the development of PFHxS-induced NAFLD. In conclusion, our study suggests that environmental exposure to PFHxS could be a potential risk factor for the development of NAFLD, challenging the earlier notion of PFHxS being safer as previously claimed. [ABSTRACT FROM AUTHOR]

Nager syndrome (NS) is a rare disease marked with craniofacial and preaxial limb anomalies. In this report, we summarized the current evidence to determine a possible genotype–phenotype association among NS individuals. Twenty-four articles comprising of 84 NS (including 9 patients with a severe form of NS [Rodriguez syndrome]) patients were examined, of which 76% were caused by variants in SF3B4 (OMIM *605593, Splicing Factor 3B, Subunit 4). Within the SF3B4 gene, variants located in exon 3 commonly occurred (20%) from a total identified variant, while hotspot location was identified in exon 1 (12%), and primarily occurred as frameshift variants (64%). Thirty-five distinct pathogenic variants within SF3B4 gene were identified with two common sites, c.1A > G and c.1060dupC in exons 1 and 5, respectively. Although no significant genotype–phenotype association was found, it is notable that patients with frameshift SF3B4 variants and predicted to lead to nonsense-mediated RNA decay (NMD) of the transcripts tended to have a more severe clinical manifestation. Additionally, patients harboring variants in exons 2 and 3 displayed a higher proportion of cardiac malformations. Taken together, this article summarizes the pathogenic variants observed in SF3B4 and provides a possible genotype–phenotype relationship in this disease. [ABSTRACT FROM AUTHOR]

Bone has multiple functions in animals, such as supporting the body for mobility. The zebrafish skeleton is composed of craniofacial and axial skeletons. It shares a physiological curvature and consists of a similar number of vertebrae as humans. Bone degeneration and malformations have been widely studied in zebrafish as human disease models. High‐resolution imaging and different bone properties such as density and volume can be obtained using micro‐computed tomography (micro‐CT). This study aimed to understand the possible changes in the structure and bone mineral density (BMD) of the vertebrae and craniofacial skeleton with age (4, 12 and 24 months post fertilisation [mpf]) in zebrafish. Our data showed that the BMD in the vertebrae and specific craniofacial skeleton (mandibular arch, ceratohyal and ethmoid plate) of 12 and 24 mpf fish were higher than that of the 4 mpf fish. In addition, we found the age‐dependent increase in BMD was not ubiquitously observed in facial bones, and such differences were not correlated with bone type. In summary, such additional information on the craniofacial skeleton could help in understanding bone development throughout the lifespan of zebrafish. [ABSTRACT FROM AUTHOR]

Treacher Collins syndrome (TCS, OMIM: 154500) is a rare congenital craniofacial disorder that is caused by variants in the genes TCOF1, POLR1D, POLR1C, and POLR1B. Studies on the association between phenotypic variability and their relative variants are very limited. This systematic review summarized the 53 literatures from PubMed and Scopus to explore the potential TCS genotype–phenotype correlations with statistical analysis. Studies reporting both complete molecular genetics and clinical data were included. We identified that the molecular anomaly within TCOF1 (88.71%) accounted for most TCS cases. The only true hot spot for TCOF1 was detected in exon 24, with recurrent c.4369_4373delAAGAA variant is identified. While the hot spot for POLR1D, POLR1C, and POLR1B were identified in exons 3, 8, and 15, respectively. Our result suggested that the higher severity level was likely to be observed in Asian patients harboring TCOF1 variants rather than POLR1. Moreover, common 5‐bp deletions tended to have a higher severity degree in comparison to any variants within exon 24 of TCOF1. In summary, this report suggested the relationship between genetic and clinical data in TCS. Our findings could be used as a reference for clinical diagnosis and further biological studies. [ABSTRACT FROM AUTHOR]

Mitochondria-rich cells (MRCs) of fish gills are well known for their roles in [Na.sup.+] and [Cl.sup.-] excretion in seawater environment. However, the level of understanding of their roles in fresh water is limited. In this study, we used the Percoll gradient technique to isolate gill MRCs from Japanese eels (Anguilla japonica Temminck and Schlegel, 1846) and measured the mRNA expression of two selected ion transporters, which were partially cloned in our laboratory: sodium bicarbonate co-transporter 1 (nbcel) and vacuolar proton pumps ([H.sup.+]-atpase). In addition, protein expressions of [H.sup.+]- ATPase and NBCe1 in whole gill were studied using Western blotting. The data indicated that both NBCe1 and [H.sup.+]-ATPase mRNA and protein expressions increased after seawater to freshwater transfer. This is the first report of changes in mRNA expression for these two ion transporters in MRCs of Japanese eels during seawater to freshwater transfer, confirming the roles of MRCs in osmoregulation in fresh water. Les cellules riches en mitochondries (MRC) des branchies de poissons jouent un role bien connu dans l'excretion de [Na.sup.+] et de [Cl.sup.-] dans le milieu marin. Cependant, leur fonction en eau douce est moins bien comprise. Nous utilisons, dans notre etude, la technique du gradient au Percoll pour isoler les MRC chez des anguilles du Japon (Anguilla japonica Temminck and Schlegel, 1846) et nous mesurons l'expression de l'ARNm de deux transporteurs d'ions selectionnes, qui ont ete partiellement clones dans notre laboratoire, le co-transporteur 1 de bicarbonate de sodium (nbcel) et les pompes vacuolaires de protons ([H.sup.+]-atpase). Nous etudions, de plus, les expressions proteiniques de [H.sup.+]-ATPase et de NBCe1 dans la branchie entiere par buvardage Western. Les donnees indiquent une augmentation des expressions d'ARNm et de proteines, tant chez NBCe1 que chez [H.sup.+]-ATPase, apres un passage de l'eau de mer a l'eau douce. C'est la premiere mention de changements de l'expression de l'ARNm chez ces deux transporteurs dans les MRC d'anguilles du Japon durant le transfert de l'eau de mer a l' eau douce, ce qui confirme les roles des MRC dans l'osmoregulation en eau douce. [Traduit par la Redaction], Introduction During seawater to freshwater adaptation, fish face the problem of osmotic influx of water and the passive efflux of ions. The gill epithelia, one the most important osmoregulatory organs [...]