Genetic Disorders Research Articles

Use of coagulation factor concentrates and blood transfusion in cardiac surgery: a retrospective cohort study of adults with hereditary and acquired bleeding disorders

BackgroundCardiac surgery poses a significant risk of perioperative bleeding and allogeneic blood transfusions, particularly in patients with bleeding disorders. Increasingly frequent use of coagulation factor concentrates could impact haemorrhagic risks, thromboembolic events, and costs. We describe the use of coagulation factor concentrates and allogeneic blood products in cardiac surgical patients with hereditary and acquired bleeding disorders to assess pertinent outcomes, including perioperative haemorrhage, thromboembolism, and hospital costs. MethodsWe conducted a retrospective cohort study using the Premier Health Database, including adult cardiac surgical patients diagnosed with hereditary or acquired bleeding disorders compared with those without bleeding disorders. ResultsPatients with acquired bleeding disorders required more extensive use of coagulation factor concentrates and blood products compared with those with hereditary bleeding disorders or without bleeding disorders. The highest exposures to coagulation factor concentrates were found in the acquired bleeding disorders group, with 24% receiving factor VIIa and 11.7% receiving prothrombin complex concentrate. This group also experienced significantly higher rates of complications, including a 15.8% rate of haemorrhage and a 19.2% rate of thromboembolic events. The acquired bleeding disorders group had longer intensive care and hospital stays, and the highest mortality rate (19.2%). The increased use of perioperative replacement of factor VIII and factor IX in the hereditary bleeding disorders group led to increased pharmacy costs but did not significantly impact blood bank charges. ConclusionsAcquired bleeding disorders in cardiac surgery patients are associated with increased use of haemostatic interventions, postoperative complications, and increased healthcare costs. Improved management of perioperative haemostasis and thromboprophylaxis strategies are essential for optimising patient outcomes and reducing expenses.

MitoQ enhances CYP19A1 expression to stimulate WNT/β-catenin signaling pathway for promoting hair growth in androgenetic alopecia.

Increased sensitivity to androgens and androgen receptors is the underlying cause of androgenetic alopecia (AGA), a hereditary disease. Our study investigated the preventive effects of MitoQ on dihydrotestosterone (DHT)-induced mitochondrial dysfunction and subsequent hair loss from three perspectives: in vivo, in vitro, and network pharmacology. A mouse model of AGA was used to assess the effectiveness of MitoQ intervention. Seventy-five drug targets and 367 disease targets were identified through network pharmacology analysis. Molecular docking analysis revealed that the androgen receptor (AR) and CYP19A1, which are key targets of MitoQ, may play a role in AGA treatment. CYP19A1 expression was downregulated in lesions from patients with AGA compared to healthy scalp tissue, while AR expression was upregulated. Cellular tests of human dermal papilla cells (DPCs) treated with MitoQ revealed that the mRNA and protein expression of AR remained unchanged, but the mRNA expression of CYP19A1 was upregulated. Our experiments also confirmed that CYP19A1 overexpression prevented DHT-induced apoptosis and upregulated the expression levels of WNT3A and β-catenin, whereas increased apoptosis levels and the downregulation of WNT3A and β-catenin due to CYP19A1 knockdown were reduced by MitoQ. We verified that MitoQ enhanced hair growth in DHT-induced hair loss model mice and reversed DHT-induced apoptosis by enhancing the expression of CYP19A1 in DPCs and that MitoQ may act by mediating the WNT/β-catenin pathway. These findings indicate that MitoQ could be a promising intervention for AGA and that CYP19A1 may serve as a valuable therapeutic target for AGA.

Human DNA Mutations and their Impact on Genetic Disorders.

DNA is a remarkably precise medium for copying and storing biological information. It serves as a design for cellular machinery that permits cells, organs, and even whole organisms to work. The fidelity of DNA replication results from the action of hundreds of genes involved in proofreading and damage repair. All human cells can acquire genetic changes in their DNA all over life. Genetic mutations are changes to the DNA sequence that happen during cell division when the cells make copies of themselves. Mutations in the DNA can cause genetic illnesses such as cancer, or they could help humans better adapt to their environment over time. The endogenous reactive metabolites, therapeutic medicines, and an excess of environmental mutagens, such as UV rays all continuously damage DNA, compromising its integrity. One or more chromosomal alterations and point mutations at a single site (monogenic mutation) including deletions, duplications, and inversions illustrate such DNA mutations. Genetic conditions can occur when an altered gene is inherited from parents, which increases the risk of developing that particular condition, or some gene alterations can happen randomly. Moreover, symptoms of genetic conditions depend on which gene has a mutation. There are many different diseases and conditions caused by mutations. Some of the most common genetic conditions are Alzheimer's disease, some cancers, cystic fibrosis, Down syndrome, and sickle cell disease. Interestingly, scientists find that DNA mutations are more common than formerly thought. This review outlines the main DNA mutations that occur along the human genome and their influence on human health. The subject of patents pertaining to DNA mutations and genetic disorders has been brought up.

Porphyrinuria in Autism Spectrum Disorder: A Review.

Numerous studies demonstrated that the number of children with autism spectrum disorder (ASD) has increased remarkably in the past decade. A portion of ASD etiology, however, is attributed to environmental issues and genetic disorders. We highlighted a scoping review to principally evaluate the current information on mercury exposure in ASD children and to reveal knowledge gaps. Elevated porphyrins concentration in the urinary system related to mercury exposure, such as precoproporphyrin (prcP), coproporphyrin (cP), and pentacarboxyporphyrin (5cxP), was shown in comparison with controls. Moreover, high levels of urinary porphyrins have been elevated in response to heavy metal exposure. The related pattern (increased prcP, cP, and 5cxP) with Hg exposure may be used as biomarkers in the characteristics of ASD symptoms. However, this review highlighted the data gaps because the control groups were not genderand age-matched for ASD children.

Genetics in Reproductive Medicine

Thanks to advances in technology, genetic testing is now available to explore the causes of infertility and to assess the risk of a given couple passing on a genetic disorder to their offspring. This allows at-risk couples to make an informed decision when opting for assisted reproduction and allows professionals to offer pre-implantation diagnosis when appropriate. Genetic screening of an infertile couple has thus become standard practice for an appropriate diagnosis, treatment, and prognostic assessment. This review aims to highlight the conditions under which genetic screening plays a role in improving reproductive outcomes for infertile couples.

Intersection of the Fragile X-related disorders and the DNA damage response

The Repeat Expansion Diseases (REDs) are a large group of human genetic disorders that result from an increase in the number of repeats in a disease-specific tandem repeat or microsatellite. Emerging evidence suggests that the repeats trigger an error-prone form of DNA repair that causes the expansion mutation by exploiting a limitation in normal mismatch repair. Furthermore, while much remains to be understood about how the mutation causes pathology in different diseases in this group, there is evidence to suggest that some of the downstream consequences of repeat expansion trigger the DNA damage response in ways that contribute to disease pathology. This review will discuss these subjects in the context of the Fragile X-related disorders (aka the FMR1 disorders) that provide a particularly interesting example of the intersection between the repeats and the DNA damage response that may also be relevant for many other diseases in this group.

Prenatal Diagnosis and Management of Generalized Arterial Calcification of Infancy

BACKGROUND: Generalized arterial calcification of infancy is a rare genetic disorder that was first reported in 1899. Since then, slightly more than 200 cases have been documented. This rare autosomal recessive disorder occurs when the homozygous ENPP1 gene mutation is associated with abnormal calcification in the medium and large arteries in the fetus. Overall mortality in individuals with generalized arterial calcification of infancy is high (55%) before the age of 6 months, with 24.4% dying in utero. Due to the high mortality rate, there is a critical need for additional reports and research regarding generalized arterial calcification of infancy. CASE: We submit a case report of a child with generalized arterial calcification of infancy—a unique instance in which the diagnosis was established prenatally and treatment was initiated in utero. Patient care was continued through a multidisciplinary approach coordinated between specialists across India, Australia, and the United States. There was an almost complete resolution of the calcification, with near-normal development and intellectual capacity of the child for age. CONCLUSION: Clear guidelines are needed regarding prenatal use of bisphosphonate therapy, timing, dosage, and duration of treatment for fetuses with ENPP1 gene mutations to minimize disease progression and improve neonatal health at birth. This case further illustrates how involving well-informed parents in decision making can help tailor the appropriate treatment. Our report also describes the possibility of new, ongoing clinical trials that may pave the way for a cure for this child and others.

TGF-β receptor-specific NanoBRET Target Engagement in living cells for high-throughput kinase inhibitor screens

Targeting transforming growth factor-β (TGF-β) receptors is a promising pharmacological approach to normalize aberrant signaling in genetic and non-genetic TGF-β associated diseases including fibrosis, cancer, cardiovascular and musculoskeletal disorders. To identify novel TGF-β receptor kinase inhibitors, methods like in vitro kinase assays, western blot or transcriptional reporter assays are often used for screening purposes. While these methods may have certain advantages, the lack of integration of key features such as receptor specificity, high-throughput capability, and cellular context resemblance remains a major disadvantage. This deficiency could ultimately hinder the translation of study outcomes into later (clinical) stages of drug development. In this study, we introduce an adjusted and optimized live cell NanoBRET Target Engagement (TE)-based method to identify TGF-β receptor specific kinase inhibitors. This comprehensive toolkit contains various TGF-β type I and type II receptors, with corresponding nanoBRET tracers, and disease-related cell lines, including novel non-commercially available materials. The nanoBRET capacity and kinase inhibitory window can be significantly enhanced for functional measurements when stable expression cell lines and substantially low tracer concentrations are used. In addition, this system can be tailored to study TGF-β associated genetic disorders and possibly be used to screen for disease-specific therapeutics. Therefore, the use of this optimized, live cell, antibody-independent nanoBRET Target Engagement assay is highly encouraged for future high-throughput compound screens targeting TGF-β/BMP receptors.

Identify Diabetes-related Targets based on ForgeNet_GPC.

Research on potential therapeutic targets and new mechanisms of action can greatly improve the efficiency of new drug development. Polygenic genetic diseases, such as diabetes, are caused by the interaction of multiple gene loci and environmental factors. In this study, a disease target identification algorithm based on protein recognition is proposed. In this method, the related and unrelated targets are collected from literature databases for treating diabetes. The transcribed proteins corresponding to each target are queried in order to construct a protein dataset. Six protein feature extraction algorithms (AAC, CKSAAGP, DDE, DPC, GAAP, and TPC) are utilized to obtain the feature vectors of each protein, which are merged into the full feature vectors. A novel classifier (forgeNet_GPC) based on forgeNet and Gaussian process classifier (GPC) is proposed to classify the proteins. In forgeNet_GPC, forgeNet is utilized to select the important features, and GPC is utilized to solve the classification problem. The experimental results reveal that forgeNet_GPC performs better than 22 classifiers in terms of ROC-AUC, PR-AUC, MCC, Youden Index, and Kappa.

Concurrent spinal schwannoma and meningioma without neurofibromatosis: case presentation and review of literature

Abstract Background Concurrent multiple tumors developing in the spinal cord are rare, except for in genetic disorders, such as neurofibromatosis and von Hippel–Lindau disease. The presence of multiple histologically different spinal tumors in the absence of NF-2 is extremely rare. Schwannoma and meningioma can be explained partly by their common origin from the same mesenchymal cell, there is currently no explanation for the simultaneous existence of different spinal tumors other than simple coincidence. Case presentation After review of literature, there are thirteen such cases reported in the literature in addition to the present case. The current patient presents with lower limb weakness, and the patient radiology revealed intradural mass opposite the fourth lumbar vertebra with contrast enhancement and intradural extramedullary mass opposite the tenth dorsal vertebra with contrast enhancement in MRI spine. The coexistence of these tumors may be coincidental or might be due to a common histological origin of the Schwann cells and the meningocytes. Conclusion Schwannoma and meningioma have different radiological characteristics and require different managing procedures such as dural base coagulation in meningiomas and rootlet sacrifice in schwannomas.

Knowledge, perception, and attitude toward premarital screening among university students in Kurdistan region–Iraq

Premarital screening programs are essential for identifying and providing counseling to couples at risk of transmitting genetic diseases or sexually transmitted infections. Despite their importance, university students’ awareness and knowledge of premarital screening programs remain inadequate. This study aimed to evaluate the knowledge, perceptions, and attitudes of university students in the Kurdistan Region of Iraq regarding premarital screening programs. A cross-sectional survey involving 960 students was conducted from December 2023 to February 2024. The survey assessed participants’ demographics, knowledge, perception, and attitudes toward PMSP using a structured questionnaire. Findings revealed that a significant portion of participants (39.4%) had poor knowledge of premarital screening programs, 35.9% had fair knowledge, and only 24.7% had good knowledge. Despite limited knowledge, there was strong support for premarital screening programs, with 83.1% agreeing on its importance and 78.8% recognizing the need for premarital awareness. Most participants (65.8%) believed premarital screening programs could reduce genetic diseases, and 65.6% thought it could lower sexually transmitted diseases’ prevalence. Cultural acceptance of marrying relatives was notable, with 59.7% disagreeing with the preference for not marrying relatives. Married participants showed significantly higher knowledge and attitude scores compared to single participants. Gender differences were observed, with males having higher knowledge scores. There were no significant differences in perception and attitude scores based on gender or residential area. The study underscores the need for enhanced educational campaigns to improve premarital screening programs awareness and positively influence attitudes, especially targeting cultural aspects like accepting relative marriages. Comprehensive education and fostering positive attitudes toward premarital screening programs are vital for their broader acceptance and implementation.

Ancestral origins of TYR and OCA2 gene mutations in oculocutaneous albinism from two admixed populations in Colombia

Autosomal recessive conditions are often associated with homozygous mutations showing common ancestral origins and are frequently linked to consanguinity. However, an increasing number of compound heterozygotes are found in diverse, admixed populations. Oculocutaneous albinism (OCA) is a recessive condition caused mainly by mutations in the TYR and OCA2 genes involved in skin pigmentation. We previously screened the TYR and OCA2 genes in Colombian OCA families, identifying both known and novel mutations. Affected family members were found to be either homozygous or compound heterozygous for these gene mutations. Compound heterozygosity, where two different recessive alleles inherited from each parent lead to the expression of an autosomal recessive trait, poses a challenge in genetic diagnosis. Estimating the ancestry of these disease-associated variants, in conjunction with understanding the colonization history of admixed populations, can enhance the precision of association mapping in genetic studies. The aim of this study was to determine the ancestral origins of TYR and OCA2 mutations for OCA patients from two populations located in the Andes region of Colombia–Altiplano Cundiboyacense and Marinilla-Santuario. Comparison of OCA patients, and their unaffected relatives, with global reference populations showed a pattern of European and Native American admixture, with little African ancestry, for these two populations. Mutation-bearing TYR and OCA2 haplotypes from Colombian OCA patients were compared against haplotypes from Spanish, Native American, and Sephardic Jewish reference populations to infer their ancestral origins. For 12 OCA1 patients from the Altiplano Cundiboyacense region, 21 out of 24 mutated TYR haplotypes show Spanish origins, two show Native American origins, and one shows a Sephardic Jewish origin. The two Native American TYR haplotypes, and the single Sephardic Jewish haplotype, are all found in compound heterozygote patients, paired with the predominant Spanish TYR haplotype G47D. OCA in these three patients is a result of genetic admixture that brought together disease-causing mutations with distinct ancestral origins. Both OCA2 patients from the Marinilla-Santuario region show homozygous OCA2 mutations with a Spanish origin. These findings underscore the complexity of the genetic architecture of Mendelian disease in admixed American populations, with both consanguinity and admixture contributing to the risk of autosomal recessive OCA in Colombia.

Sclerotic Fibroma in a Patient with Birt-Hogg-Dubé Syndrome

Birt-Hogg-Dubé syndrome (BHD) is a rare genetic disorder characterized by cutaneous lesions and systemic findings such as renal neoplasms, pulmonary cysts, and spontaneous pneumothoraces. Fibrofolliculomas, trichodiscomas, and acrochordons are the most common cutaneous lesions associated with BHD. Some cases with mucocutaneous lesions have also been reported. We report a sclerotic fibroma that developed over a previous thoracotomy scar of a patient with BHD.

In vivo photoreceptor base editing ameliorates rhodopsin-E150K autosomal-recessive retinitis pigmentosa in mice

Rhodopsin, the prototypical class-A G-protein coupled receptor, is a highly sensitive receptor for light that enables phototransduction in rod photoreceptors. Rhodopsin plays not only a sensory role but also a structural role as a major component of the rod outer segment disc, comprising over 90% of the protein content of the disc membrane. Mutations in RHO which lead to structural or functional abnormalities, including the autosomal recessive E150K mutation, result in rod dysfunction and death. Therefore, correction of deleterious rhodopsin mutations could rescue inherited retinal degeneration, as demonstrated for other visual genes such as RPE65 and PDE6B. In this study, we describe a CRISPR/Cas9 adenine base editing strategy to correct the E150K mutation and demonstrate precise in vivo editing in a Rho -E150K mouse model of autosomal recessive retinitis pigmentosa (RP). Using ultraviolet-visible spectroscopy, mass spectrometry, and the G-protein activation assay, we characterized wild-type rhodopsin and rhodopsin variants containing bystander base edits. Subretinal injection of dual-adeno-associated viruses delivering our base editing strategy yielded up to 44% Rho correction in homozygous Rho -E150K mice. Injection at postnatal day 15, but not later time points, restored rhodopsin expression, partially rescued retinal function, and partially preserved retinal structure. These findings demonstrate that in vivo base editing can restore the function of mutated structural and functional proteins in animal models of disease, including rhodopsin-associated RP and suggest that the timing of gene-editing is a crucial determinant of successful treatment outcomes for degenerative genetic diseases.

Orthopedic Surgery in Osteogenesis Imperfecta in Adults.

Osteogenesis imperfecta is a genetic disorder, mainly characterized by bone fragility. In adult with osteogenesis imperfecta, surgical treatment may be indicated as an emergency procedure in the event of a fracture, or as a scheduled procedure in case of patient functional impairment due to many causes, such as persistent pain, complex bone deformities, and degenerative arthropathies. In all cases, a multidisciplinary approach is recommended. It is essential to consider the patient's characteristics and expectations regarding treatment, as well as the local conditions, which may be complex due to the poor bone quality, bone deformity, and the presence of hardware implanted during childhood. The procedure can be very complex and challenging and each patient is a unique case. An accurate preoperative planning is mandatory to select the appropriate surgical technique, which can be either conservative or prosthetic, and to evaluate its feasibility and the risk-benefit ratio. The aim is to improve the patient's quality of life and autonomy as long as possible.

Neurodegenerative biomarkers and inflammation in patients with propionic and methylmalonic acidemias: effect of L-carnitine treatment.

Propionic and methylmalonic acidemias (PAcidemia and MMAcidemia, respectively) are genetic disorders characterized by acute metabolic decompensation and neurological complications. L-carnitine (LC) is effective in reducing toxic metabolites that are related to the pathophysiology of these diseases. Therefore we investigated biomarkers of inflammation (cytokines and C-reactive protein (CRP)), neurodegeneration (BDNF, NCAM-1 and cathepsin-D) and biomolecules oxidation (sulfhydryl content and thiobarbituric acid-reactive species (TBARS)), as well as carnitine concentrations in untreated patients with PAcidemia and MMAcidemia, in patients under treatment with LC and a protein-restricted diet for until 2 years and in patients under the same treatment for more than 2 years. It was verified an increase of CRP, IL-6, IL-8, TNF-α, IL-10, NCAM-1 and cathepsin-D in untreated patients compared to controls. On the other hand, reduced levels of TNF-α, CRP, IL-10, NCAM-1 and cathepsin-D were found in plasma from treated patients, as well as increased concentrations of LC. Furthermore, oxidative biomarkers were increased in untreated patients and were normalized with the prolonged treatment with LC. In conclusion, this work shows, for the first time, that inflammatory and neurodegenerative peripheral biomarkers are increased in patients with PAcidemia and MMAcidemia and that treatment with LC is effective to protect against these alterations.

External Occipital Protuberance Enlargement in Children: A Benign Anatomic Variant with Rare Associations

Objective − The aim of this study is to raise awareness about External Occipital Protuberance (EOP) enlargement in children, its typically benign anatomical variant, and the importance of considering associated conditions in diagnosis and management.Case Report − We reviewed the cases of four male patients, presenting with EOP enlargement. Among the cases, one involved a newborn diagnosed with Menkes disease, a rare genetic disorder affecting copper transport, which was associated with occipital exostosis. The other three cases involved adolescents with varying degrees of EOP enlargement, linked to factors such as prior trauma and excessive screen time. Conclusion − While EOP enlargement is generally a benign anatomical variant, this study underscores the importance of differential diagnosis, particularly in the pediatric population. Clinicians should be aware of the potential, albeit rare, associations with serious conditions such as Menkes disease. A comprehensive approach to diagnosis and management is recommended, especially in symptomatic cases.

Exploring 17q12 Deletion Syndrome: A Case Report of Neurodevelopmental, Endocrine, and Genital Anomalies

Objective − 17q12 deletion syndrome is a rare genetic disease characterized by neurodevelopmental disorders, genital and renal abnormalities, and maturity-onset diabetes of the young type 5 (MODY5).Case Report − This case report details the case of a 13-year-old female with moderate intellectual disability, Mayer-Rokitansky-Küster-Hauser syndrome, multicystic dysplastic kidneys, and MODY5. Genetic testing revealed a 1.52-megabase heterozygous deletion on chromosome 17q12, encompassing the HNF1B and LHX1 genes, which was found to be inherited from the mother. Conclusion − This case underscores the importance of early genetic testing and multidisciplinary approach in managing the multisystemic manifestations of 17q12 deletion syndrome. Early diagnosis and appropriate management are crucial for improving the outcomes and quality of life for affected individuals.

Non-invasive prenatal detection of dominant single-gene disorders in fetal structural abnormalities: a clinical feasibility study.

This study evaluated the accuracy of non-invasive prenatal testing (NIPT-SGDs) for dominant monogenic genetic diseases associated with fetal structural abnormalities and to assess the feasibility of clinical application. Pregnant women requiring prenatal diagnosis due to fetal structural abnormalities were enrolled. Maternal peripheral blood was analyzed for cell-free DNA (cfDNA) using coordinative allele-aware target enrichment sequencing (COATE-seq). This assessed fetal allele depth distribution, fraction and variation ratio. The variation's origin was then determined to obtain fetal variation information. Finally, NIPT-SGDs results were confirmed via invasive prenatal diagnosis (IPD). Upon examination of 113 samples using NIPT-SGDs, COATE-seq successfully analyzed 112 for fetal variation, excluding one due to hemolysis. The study detected six positive cases, yielding a 5.36% detection rate. These disorders included tuberous sclerosis complex (TSC1 and TSC2 being its causative genes), Noonan syndrome (PTPN11), polycystic kidney disease (PKD1), and Kabuki syndrome (KMT2D), occurring twice each, except for Noonan and polycystic kidney disease. Two false positives were due to the mother being a genetic mosaicism. Compared to invasive whole-exome sequencing (WES), NIPT-SGDs did not detect nine positive cases of IPD dominant monogenic diseases, accurately identifying 90.18% (101/112) of the actual positive and negative cases. Our findings demonstrate the clinical utility of NIPT-SGDs using COATE-seq in effectively identifying fetuses with dominant single-gene disorders. Furthermore, this method can be applied to all fetuses.

Endurance exercise attenuates Gαq-RNAi induced hereditary obesity and skeletal muscle dysfunction via improving skeletal muscle Srl/MRCC-I pathway in Drosophila.

G protein alpha q subunit (Gαq) can binds to the G protein-coupled receptor (GPCR) for signaling and is closely related to lipid metabolism. Endurance exercise is an effective means of combating acquired obesity and its complications, but the mechanisms by which endurance exercise modulates hereditary obesity and its complications are unknown. In this study, we achieved knockdown of Gαq in drosophila adipose tissue and skeletal muscle by constructing the Gαq-UAS-RNAi/Ppl-Gal4 and Gαq-UAS-RNAi/Mef2-GAl4 systems. Drosophila were subjected a three-week endurance exercise intervention, and changes in relevant indicators were detected and observed by RT-PCR, ELISA, oil red staining, immunofluorescence staining, and transmission electron microscopy. The results showed that knockdown of Gαq in both adipose tissue and skeletal muscle induced a significant increase in triglycerides accompanied by a decrease in rapid climbing ability, a decrease in Superoxide Dismutase (SOD) activity level, and a decrease in Mitochondrial respiratory chain complexI (MRCC I) content in Drosophila whole body and skeletal muscle, and down-regulated the expression of the G protein alpha q subunit (Gαq), the skeletal muscle myosin heavy chain expression gene (Mhc), mitochondrial biogenesis gene Spargal(the PGC-1alpha homologue in Drosophila). Endurance exercise significantly improved the triglyceride levels in the whole body and skeletal muscle of drosophila with Gαq knockdown in adipose tissue and skeletal muscle, as well as their ability to climb, increased SOD activity level and MRCCI content level, and up-regulated the expression of Gαq, Mhc, and Spargal(Srl). Thus, the present findings suggest that genetic defects in the Gαq gene in adipose and skeletal muscle tissues induce hereditary obesity and skeletal muscle dysfunction, and that endurance exercise attenuates this hereditary obesity and concomitant skeletal muscle dysfunction in drosophila by improving skeletal muscle fiber contractile proteins, mitochondrial function and function, and antioxidant capacity via mediating the Gαq/Mhc, Gαq/Srl/MRCC-I, and Gαq/SOD pathways.