GAPO syndrome is a rare genetic condition caused by bi-allelic variants in ANTXR1 gene & is an abbreviation for its core features - growth retardation, alopecia, pseudo-anodontia & optic atrophy. Certain additional features involving various other systems have been reported over the years & contribute to the expanding spectrum of this evolving phenotype. We report GAPO syndrome in a 3.75 year old Indian female child, who presented with some unique features such as sagittal craniosynostosis with scaphocephaly & bilateral choroid plexus cysts, alongside the core phenotype. We also report a novel frameshift variant in our patient & offer first evidence for the prenatal onset of some features.

OBJECTIVE: This meta-analysis aimed to comprehensively evaluate the diagnostic use of erythrocyte membrane protein band 4.1like3 (EPB41L3) methylation detection in cervical cancer (CC) and its precancerous lesions.
METHODS: CNKI, Wanfang, Cochrane Library, PubMed, and Ovid databases were searched using a combination of subject headings and free words. Pertinent data were retrieved after screening for inclusion and exclusion criteria, and the quality of the included studies was evaluated using QUADAS-2 criteria. The appropriate software was used for heterogeneity analysis and combined effect size calculation. Additionally, sensitivity analysis was used to evaluate the robustness of the combined results, and meta-regression and subgroup analysis were conducted to investigate the origins of heterogeneity.
RESULTS: This meta-analysis included six studies, including 525 healthy individuals, 182 cervical intraepithelial neoplasia 1 (CIN1) samples, 182 CIN2 samples, 281 CIN3 samples, and 226 CC samples. EPB41L3 methylation detection for CIN2 and above lesions demonstrated combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and the area under the curve of the comprehensive receiver operating characteristic curve of 0.67, 0.76, 3.19, 0.41, 7.60, and 0.80, respectively; CIN3 and above lesions demonstrated these evaluations at 0.73, 0.84, 4.35, 0.33, 23.94, and 0.90, respectively. Meta-regression analysis revealed that the population, time, sample type, detection method, literature quality, and sample size were not significant sources of heterogeneity affecting the combined diagnostic efficacy of CIN2 and above lesions (p > 0.05). Subgroup analysis revealed higher combined diagnostic values of CIN2 and above lesions in retrospective studies, tissue samples, and Chinese populations, with DORs of 41.03, 14.59, and 13.70, respectively.
CONCLUSIONS: EPB41L3 methylation demonstrated a relatively low diagnostic performance in CC and precancerous lesions. However, it merits further investigation as a potential biomarker. Integrating it with multiple gene detection, human papillomavirus testing, and ThinPrep liquid-based cytology test examination is recommended to explore improved diagnostic strategies for CC and its precancerous lesions.

Adipokines play a significant role in cardiometabolic diseases. Asprosin, a newly discovered adipokine, was first identified as a glucose-raising protein hormone. Asprosin also stimulates appetite and regulates glucose and lipid metabolism. Its identified receptors so far include Olfr734 and Ptprd. Clinical studies have found that asprosin may be associated with cardiometabolic diseases. Asprosin may have diagnostic and therapeutic potential in obesity, diabetes, metabolic syndrome and atherosclerotic cardiovascular diseases. Herein, the structure, receptors, and functions of asprosin and its relationship with cardiometabolic diseases are summarized based on recent findings.

Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with severe social communication, interaction, and sensory processing impairments. Efforts to understand its etiology and pathophysiology are crucial for improving treatment and prevention measures. Preclinical models of ASD are essential for investigating the biological mechanisms and should present translatability potential. We aim to evaluate the consistency of the most commonly used rodent models of ASD in displaying autistic-like behavior through a systematic review and meta-analysis.
This review will focus on the most frequently used autism models, surveying studies of six genetic (Ube3a, Pten, Nlgn3, Shank3, Mecp2, and Fmr1), three chemically induced (valproic acid (VPA), lipopolysaccharide (LPS), and polyinosinic:polycytidylic acid (poly(I:C))), and one inbred model (BTBR T+ Itpr3tf/J mouse strain). Two independent reviewers will screen the records. Data extraction of behavioral outcomes and risk of bias evaluation will be performed. We will conduct a meta-analysis whenever at least five studies investigate the same model and behavioral outcome. We will also explore the heterogeneity and publication bias. Network meta-analyses are planned to compare different models.
By shortening the gap between animal behavior and human endophenotypes or specific clinical symptoms, we expect to help researchers on which rodent models are adequate for research of specific behavioral manifestations of autism, which potentially require a combination of them depending on the research interest.
PROSPERO CRD42021226299 .

Many individuals diagnosed with autism spectrum disorder (ASD) experience gastrointestinal (GI) dysfunction and show microbial dysbiosis. Variation in gut microbial populations is associated with increased risk for GI symptoms such as chronic constipation and diarrhoea, which decrease quality of life. Several preclinical models of autism also demonstrate microbial dysbiosis. Given that much pre-clinical research is conducted in mouse models, it is important to understand the similarities and differences between the gut microbiome in humans and these models in the context of autism. We conducted a systematic review of the literature using PubMed, ProQuest and Scopus databases to compare microbiome profiles of patients with autism and transgenic (NL3R451C, Shank3 KO, 15q dup), phenotype-first (BTBR) and environmental (Poly I:C, Maternal Inflammation Activation (MIA), valproate) mouse models of autism. Overall, we report changes in fecal microbial communities relevant to ASD based on both clinical and preclinical studies. Here, we identify an overlapping cluster of genera that are modified in both fecal samples from individuals with ASD and mouse models of autism. Specifically, we describe an increased abundance of Bilophila, Clostridium, Dorea and Lactobacillus and a decrease in Blautia genera in both humans and rodents relevant to this disorder. Studies in both humans and mice highlighted multidirectional changes in abundance (i.e. in some cases increased abundance whereas other reports showed decreases) for several genera including Akkermansia, Bacteroides, Bifidobacterium, Parabacteroides and Prevotella, suggesting that these genera may be susceptible to modification in autism. Identification of these microbial profiles may assist in characterising underlying biological mechanisms involving host-microbe interactions and provide future therapeutic targets for improving gut health in autism.

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy characterised by a high clinical and genetic heterogeneity. While most cases were described in populations with Caucasian ancestry, genetic research on CMT in Africa is scant. Only a few cases of CMT have been reported, mainly from North Africa. The current study aimed to summarise available data on CMT in Africa, with emphasis on the epidemiological, clinical, and genetic features.
We searched PubMed, Scopus, Web of Sciences, and the African Journal Online for articles published from the database inception until April 2021 using specific keywords. A total of 398 articles were screened, and 28 fulfilled our selection criteria.
A total of 107 families totalling 185 patients were reported. Most studies were reported from North Africa (n = 22). The demyelinating form of CMT was the commonest subtype, and the phenotype varied greatly between families, and one family (1%) of CMT associated with hearing impairment was reported. The inheritance pattern was autosomal recessive in 91.2% (n = 97/107) of families. CMT-associated variants were reported in 11 genes: LMNA, GDAP1, GJB1, MPZ, MTMR13, MTMR2, PRX, FGD4/FRABIN, PMP22, SH3TC2, and GARS. The most common genes reported are LMNA, GDAP1, and SH3TC2 and have been found mostly in Northern African populations.
This study reveals that CMT is not rare in Africa, and describes the current clinical and genetic profile. The review emphasised the urgent need to invest in genetic research to inform counselling, prevention, and care for CMT in numerous settings on the continent.

White adipose tissue is a dynamic endocrine organ that releases an array of adipokines, which play a key role in regulating metabolic homeostasis and multiple other physiological processes. An altered adipokine secretion profile from adipose tissue depots frequently characterizes obesity and related cardio-metabolic diseases. Asprosin is a recently discovered adipokine that is released in response to fasting. Following secretion, asprosin acts - via an olfactory G-protein coupled receptor and potentially via other unknown receptor(s) - on hepatocytes and agouti-related peptide-expressing neurons in the central nervous system to stimulate glucose secretion and promote appetite, respectively. A growing body of both in vitro and in vivo studies have shown asprosin to exert a number of effects on different metabolic tissues. Indeed, asprosin can attenuate insulin signalling and promote insulin resistance in skeletal muscle by increasing inflammation and endoplasmic reticulum stress. Interestingly, asprosin may also play a protective role in cardiomyocytes that are exposed to hypoxic conditions. Moreover, clinical studies have reported elevated circulating asprosin levels in obesity, type 2 diabetes and other obesity-related cardio-metabolic diseases, with significant associations to clinically relevant parameters. Understanding the spectrum of the effects of this novel adipokine is essential in order to determine its physiologic role and its significance as a potential therapeutic target and/or a biomarker of cardio-metabolic disease. The present review offers a comprehensive overview of the published literature on asprosin, including both clinical and preclinical studies, focusing on its role in metabolism and cardio-metabolic disease.

OBJECTIVE: There is a need to identify genetic factors that may produce coronary artery atherosclerotic disease (CAD) that are not involved in the usual risk factors leading to CAD. Previous studies have often equated coronary artery calcification (CAC) with CAD with coronary stenosis or its sequelae. The objective of this study was to examine the relationship between phosphatase and actin regulator 1 (PHACTR1) single nucleotide polymorphisms (SNPs) and the type of coronary artery disease CAD versus CAC.
METHODS: A systematic review of the literature was conducted to answer the question of whether PHACTR1 gene polymorphisms are associated with coronary artery disease expressed as coronary artery atherosclerosis or CAC.
RESULTS: Eighteen studies spanning seven PHACTR1 SNPs were identified and evaluated for the relationship between PHACTR1 and coronary artery disease. There were significant relationships between rs9349379, rs12526453, and CAD with odds ratios (ORs) (confidence interval) of, respectively, 1.15 (1.13-1.17), 1.13 (1.09-1.17) but not for rs2026458, 1.03 (0.88-1.19). The OR for CAC was 1.22 (1.18-1.26) for rs9349379 and 1.28 (1.21-1.38) for rs12526453.
CONCLUSIONS: Several PHACTR1 specifically rs9349379 and rs12526453 polymorphisms but not rs2026458, are associated with CAD. There are differences in the association of PHACTR1 SNPs with CAC. PHACTR1 warrants more attention and study for the prevention and treatment of CAD.

A solitary fibrous tumor (SFT) is a rare, NAB2-STAT6 fusion gene-associated mesenchymal neoplasm. It most commonly arises in the pleural site, but it can occur at many other sites, and rarely also in the head and neck (H&N) region. STFs may show many growth patterns and therefore can be easily mistaken for other more common H&N spindle cell or epithelial lesions. In this study, we present our experience in the diagnosis of 20 cases of SFT in the H&N region and discuss their most notable mimickers. In all cases, STAT6 expression was found positive by immunohistochemistry, and the NAB2-STAT6 fusion was confirmed by next-generation sequencing. Three major fusion variants were detected: NAB2ex2-STAT6int1 (5/20, 25%), NAB2ex6-STAT6ex16 (4/20, 20%), and NAB2ex4-STAT6ex2 (3/20, 15%). Clinical follow-up was available for 16 patients (median follow-up time: 84 months). One patient with a morphologically malignant SFT experienced multiple local recurrences, followed by dissemination into the lungs and meninges. This malignant SFT also displayed an aberrant FLI1 expression, which was not previously reported in SFT cases. We also summarize findings from 200 cases of SFT of the H&N region, which included cases from our study, and from previous studies that reported on the fusion status of the STAT6 gene. The results suggest that metastatic disease developed only in cases with STAT6 variants that included the DNA-binding domain (STAT6-full variants), which contradicts expectations from previous reports and deserves further investigation.

This report describes siblings with Stromme syndrome, a rare genetic condition that primarily presents with a triad of intestinal atresia, cranial and ocular malformations, and other organ systems could be involved. This clinical triad was initially named after the first person to describe it in 1993. Here, we report a family with two siblings who presented with unusual intestinal atresia and ocular and CNS abnormalities. The first patient is a 6-year-old-boy with apple peel duodeno-jejunal atresia, unilateral microphthalmia and microcephaly. The second patient, a younger brother, presented with intestinal atresia, corneal opacity and alobar holoprosencephaly and passed away at the age of 3 months. Exome sequencing showed a novel homozygous variant in the CENPF gene, NM_016343.3: c.1195-2 A > G that was detected in both of the affected siblings. This is a report and literature review of CENPF-related ciliopathy, which may result in Stromme syndrome. As this is the fourth report linking the CENPF gene variant with Stromme syndrome and first reported case presented with holoprosencephaly, it will expand the current knowledge on the genotype and the phenotype of Stromme syndrome.