Search Results (145)

Inherited epidermolysis bullosa (EB) is a heterogeneous clinical entity that includes over 30 phenotypically and/or genotypically distinct inherited disorders, characterized by mechanical skin fragility and bullae formation. Junctional EB (JEB) is an autosomal recessive disease characterized by an intermediated cleavage level within the skin layers, commonly at the “lamina lucida”. Laryngo-onycho-cutaneous syndrome (LOC) is an extremely rare variant of JEB, characterized by granulation tissue formation in specific body sites (skin, larynx, and nails). Although most cases of JEB are caused by pathogenic variants occurring in the genes encoding for classical components of the lamina lucida, such as laminin 332 (LAMA3, LAMB3, LAMC2), integrin α6β4 (ITGA6, ITGB4), and collagen XVII (COL17A1), other variants have also been described. We report the case of a 4-month-old male infant who presented with recurrent bullous and erosive lesions from the first month of life. At the first dermatological evaluation, the patient was agitated and exhibited hoarse breathing, a clinical sign suggestive of laryngeal involvement. Multiple polygonal skin erosions were observed on the cheeks, along with similar isolated, roundish lesions on the scalp and legs. Notably, nail dystrophy and near-complete anonychia were evident on the left first and fifth toes. Due to the coexistence of skin erosions and nail dystrophy in such a young infant, a congenital bullous disorder was suspected, prompting molecular analysis of all potentially involved genes. In the patient’s DNA, clinical exome sequencing (CES) identified a pathogenic variant, apparently in homozygosity, in the exon 1 of the LAMA3 gene (18q11.2; NM_000227.6): c.47G > A;p.Trp16*. The presence of this variant was confirmed, in heterozygosity, in the genomic DNA of the patient’s mother, while it was absent in the father’s DNA. Subsequently, trio-based SNP array analysis was performed, revealing a paternally derived pathogenic microdeletion encompassing the LAMA3 locus (18q11.2). To our knowledge, this is the first reported case of JEB with a LOC-like phenotype caused by a maternally inherited monoallelic nonsense mutation in LAMA3, unmasked by an almost complete deletion of the paternal allele. The combined use of exome sequencing and SNP array is proving essential for elucidating autosomal recessive diseases with a discordant segregation. This is pivotal for providing accurate genetic counseling to parents regarding future pregnancies. Full article

Potato common scab is one of the major diseases posing a threat to potato production on a global scale. No chemical agents have been found to effectively control the occurrence of this disease, and research on the identification of resistance genes and the development of molecular markers remains relatively limited. In this study, a diploid potato variety H535, which exhibits resistance to the predominant pathogen Streptomyces scabies, was utilized as the male parent, whereas the susceptible diploid potato variety H012 served as the female parent. Building upon the resistance QTL intervals pinpointed through a genome-wide association study, two potential resistance loci were localized on chromosome 2 of the potato genome, spanning the regions between 38–38.6 Mb and 41.3–42.7 Mb. These intervals accounted for 18.03% of the total phenotypic variance and are presumed to be the primary QTLs underlying scab resistance. Building upon this foundation, we expanded the hybrid progeny population, conducted resistance assessments, selected individuals with extreme phenotypes, developed molecular markers, and conducted fine mapping of the resistance gene. A phenotypic evaluation of scab resistance was carried out using a pot-based inoculation test on 175 potato hybrid progenies to characterize the F1 generation population. Twenty lines exhibiting high resistance and thirty lines displaying high susceptibility were selected for investigations. Within the preliminary mapping interval on potato chromosome 2 (spanning 38–43 Mb), a total of 214 SSR (Simple Sequence Repeat) and 133 InDel (Insertion/Deletion) primer pairs were designed. Initial screening with parental lines identified 18 polymorphic markers (8 SSR and 10 InDel) that demonstrated stable segregation patterns. Validation using bulked segregant analysis revealed that 3 SSR markers (with 70–90% linkage) and 6 InDel markers (with 70–90% linkage) exhibited significant co-segregation with the resistance trait. A high-density genetic linkage map spanning 104.59 cm was constructed using 18 polymorphic markers, with an average marker spacing of 5.81 cm. Through linkage analysis, the resistance locus was precisely mapped to a 767 kb interval (41.33–42.09 Mb) on potato chromosome 2, flanked by SSR-2-9 and InDel-3-9. Within this refined interval, four candidate disease resistance genes were identified: RHC02H2G2507, RHC02H2G2515, PGSC0003DMG400030643, and PGSC0003DMG400030661. This study offers novel insights into the genetic architecture underlying scab resistance in potato. The high-resolution mapping results and characterized markers will facilitate marker-assisted selection (MAS) in disease resistance breeding programs, providing an efficient strategy for developing cultivars with enhanced resistance to Streptomyces scabies. Full article

Cyvirus cyprinidallo2 (CyHV-2) is the causative agent of herpesviral hematopoietic necrosis in several economically important farmed freshwater fish species of the genus Carassius. Despite several CyHV-2 strains being isolated and fully sequenced, there is a lack of detailed characterization and consistent information on strains that exhibit high virulence in adult goldfish through viral challenge by immersion, particularly in the context of European strains and host populations. Strains that can cause highly virulent disease via this inoculation route are much more compatible with experimental designs that are representative of natural infection; thus, their utilization provides greater biological relevance. Consequently, in this study, we isolated three novel strains of CyHV-2 (designated NL-1, NL-2, and NL-3), originating from outbreaks in The Netherlands. Full-length genome sequencing and phylogenetic analyses revealed that these newly isolated strains are distinct from known strains and from each other. Significant differences were observed between the strains, in terms of in vitro growth kinetics, with NL-2 exhibiting stable passaging and superior fitness in vitro. Importantly, the challenge of adult Shubunkin goldfish with the NL-2 strain via immersion (2000 PFU/mL) induced an average mortality of ~40%, while parallel experiments with the CyHV-2 reference strain ST-J1 resulted in no mortality. Taken together, this study represents the characterization of a new CyHV-2 in vivo infection model, much more compatible with experimental designs that are required to be representative of natural infection. This model will be extremely useful in many aspects of CyHV-2 research in the future. Importantly, the genetic and phenotypic characterization performed in this study generates hypotheses on the potential roles of CyHV-2 genes in adaptation of the virus in vitro or in vivo. Full article

The exploration of Streptomyces from extreme environments presents a particularly compelling avenue for novel compound discovery. A Gram-positive, pink-pigmented Streptomyces strain designated HC307^T was isolated from a soil sample collected in Xizang (Tibet), China. The exploration of Streptomyces from extreme environments presents a particularly compelling avenue for novel compound discovery. In this study, the 16S rRNA sequence of strain HC307^T exhibited the highest similarity with Streptomyces prasinosporus NRRL B-12431^T (97.5%) and Streptomyces chromofuscus DSM 40273^T (97.3%), which were below 98.7%. The draft genome of the bacteria was 10.0 Mb, with a G+C content of 70.0 mol%. The average nucleotide identity (ANI) values of strain HC307^T and similar type strains ranged from 78.3% to 87.5% (<95%). The digital DNA-DNA hybridization (dDDH) values ranged from 22.6% to 33.9% (<70%), which was consistent with the results obtained from phylogenetic tree analysis. Phenotypically, this bacterium grew within the temperature range of 25–40 °C, at a pH range of 5 to 9, and in NaCl concentrations from 0% to 6% (w/v). The polar lipid profile of strain HC307^T was diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and unidentified lipids. The analysis of 32 biosynthetic gene clusters (BGCs) indicated the strain’s capacity to synthesize diverse compounds. Phylogenetic and phenotypic analyses demonstrated that strain HC307^T represented a novel species within the genus Streptomyces, and proposed the name Streptomyces flavusporus sp. nov., with strain HC307^T (=DSM 35222^T=CGMCC 32047^T). The strain was deposited in Deutsche Sammlung von Mikroorganismen und Zellkulturen and the China General Microbiological Culture Collection Center for patent procedures under the Budapest Treaty. Full article

Background: The alarming increase in carbapenemase-producing Enterobacterales is a matter of grave public health concern. The most ubiquitous carbapenemases, Klebsiella pneumoniae carbapenemase (KPC)-, New Delhi metallo-β-lactamase (NDM)-, and oxacillinase (OXA-48)-like enzymes, belong to the Ambler molecular classes A, B, and D, respectively. KPC- and OXA-48-like enzymes have a serine-based hydrolytic mechanism, while NDMs are metallo-β-lactamases that contain zinc in the active site. For the judicious use of reserve drugs and promoting antimicrobial stewardship, timely detection of carbapenemases is essential. While molecular tools are the gold standard for the detection of these enzymes, many laboratories have limited access to them. This study focused on evaluating in-house tools and commercial phenotypic tests for the detection of OXA-48-, KPC-, and NDM-like enzymes in K. pneumoniae, the predominant extremely drug-resistant pathogen in Oman. Methods: In total, 80 GeneXpert/PCR-confirmed (40 OXA-48 and 20 KPC and NDM each) and 37 whole-genome-sequenced (25 OXA-232 and 6 KPC-2, plus NDM-1 and NDM-5) K. pneumoniae were subjected to screening by temocillin (30 μg disk) (MAST Diagnostica, Germany) and D71C (MASTDISCS^®). Isolates resistant to temocillin (<11 mm) and D71C were subjected to four tests: an in-house tool (OXA-48 disk test) and three commercial phenotypic tests: (i) the MASTDISCS^® Combi (D72C) (MAST Group Ltd., Bootle, UK); (ii) the MASTDISCS^® Combi (D73C) (MAST Group Ltd., UK); and (iii) an immunochromatographic assay (ICT), which is the KPC/IMP/NDM/VIM/OXA-48 Combo test kit (Medomics, China), for the detection of OXA-48-, KPC-, and NDM-like carbapenemases. Results: Temocillin exhibited good sensitivity and specificity (100% and 97.50%) compared to D71C (70% and 100%). Among the confirmatory tests, the in-house OXA-48 disk test had 92.50% sensitivity and 100% specificity, while the commercial MAST DISC tests D72C, D73C, and ICT had 97.50%, 95.00%, and 100% sensitivity and 100%, 91.67%, and 95% specificity, respectively. Conclusions: The temocillin disk test is a good screening tool. With high sensitivity and specificity, ease of performance, short turnaround time, and low cost, we recommend the ICT format for routine diagnostic use. In resource-constrained centers, the OXA-48 disk test is an excellent alternative with high sensitivity and specificity. Full article

Background: Uniparental disomy (UPD) is the inheritance of both copies of a chromosome from a single parent, leading to distinct genetic conditions. Maternal UPD of chromosome 6 (UPD(6)mat) is extremely rare, with few molecularly confirmed cases reported. Methods: We report a prematurely born female with isodisomic UPD(6)mat, presenting with intrauterine growth restriction (IUGR), developmental delay, autism spectrum disorder, dysmorphic features, and a sacrococcygeal teratoma. In addition, we reviewed 24 confirmed UPD(6)mat cases to assess clinical patterns in prenatal findings, birth outcomes, and postnatal features. Results: Trio whole-exome sequencing revealed complete isodisomy of chromosome 6 and a de novo heterozygous DIAPH2 variant of uncertain significance. In the literature review, IUGR was present in 87% of cases, with most individuals born small for gestational age and preterm. Failure to thrive and neurodevelopmental issues were also frequent. While the exact molecular basis remains unknown, imprinting disturbances—similar to those in UPD(6)pat—and cryptic trisomy 6 mosaicism, particularly in heterodisomy, are the most likely mechanisms. No specific gene or consistent epigenetic abnormality has been identified. Conclusions: This study aims to enhance the understanding of the genetic and phenotypic spectrum of UPD(6)mat, improving diagnostic and management approaches for this ultra-rare genetic disorder. We propose a detailed list of clinical assessments and tests to be performed following the detection of maternal uniparental disomy of chromosome 6. Full article

Background: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder characterized by extreme hypertriglyceridemia (>1000 mg/dL), recurrent pancreatitis, and lipoprotein lipase (LPL) deficiency. Mutations in the LMF1 gene, encoding a chaperone protein required for LPL maturation, can lead to combined lipase deficiency. This study reports a case of a 33-year-old Ecuadorian mestizo woman presenting with recurrent pancreatitis secondary to severe hypertriglyceridemia, in whom two LMF1 variants of uncertain significance (VUS) were identified. Methods: Whole-exome sequencing (WES) was performed on the patient and her asymptomatic son using next-generation sequencing (NGS). Data analysis included computational pathogenicity predictors (REVEL, PolyPhen, SIFT, MutationTaster, etc.). Two LMF1 variants—c.1142C>T (p.Pro381Leu) and c.897G>A (p.Gln299Gln)—were identified. Their pathogenic potential was assessed based on allele frequency (gnomAD), bioinformatics predictions, and ACMG criteria. Results: Both variants were classified as VUS, with c.897G>A predicted to affect splicing, potentially leading to loss of function. The c.1142C>T (p.Pro381Leu) variant, despite its low frequency, remains unclassified due to insufficient evidence. The patient’s son carried one variant but was asymptomatic. The patient’s phenotype suggested an intermediate form between monogenic and polygenic hypertriglyceridemia. Conclusions: This is a new Ecuadorian report of LMF1-related hypertriglyceridemia, highlighting the need for functional studies to confirm pathogenicity. Given the classification of both variants as VUS, further research is required to elucidate their clinical significance. This case underscores the necessity of a combined genetic and biochemical approach for diagnosing and managing severe hypertriglyceridemia. Full article

Background: The fitness costs (FCs) of antimicrobial resistance (AMR) are crucial issues in antimicrobial resistance (AMR) onset, spread, and, consequently, public health. In Staphylococcus aureus, AMR can induce significant FCs due to slow growth, low competitiveness, and virulence. Here, we investigated the genomics and FCs emerging for progressively acquiring daptomycin (DAP) and glycopeptide (GLY) reduced susceptibility in MRSA. Methods: Genomics was carried out using Illumina-MiSeq Whole-genome sequencing and bioinformatics. The biological FCs of isogenic MRSA strain pairs progressively acquiring DAP and GLY-reduced susceptibility, under DAP/GLY mono or combined therapy, were performed by in-vitro independent and competitive mixed growth, phenotypic in-vitro virulence analysis, and in-vivo G. mellonella larvae killing. Results: Genomics evidenced four different extremely resistant high-risk clones, i.e., ST-5 N315 HA-MRSA, ST-398 LA-MRSA, ST-22 USA-100 HA-EMRSA-15, and ST-1 MW2 CA-MRSA. In-vitro fitness assays revealed slow growth, lower competitiveness, and reduced virulence, predominantly in Galleria mellonella killing ability, in DAP-S hGISA, DAP-R GSSA, DAP-R hGISA, and DAP-R GISA strains. Conclusions: The occurrence of glycopeptide and daptomycin reduced susceptibility conferred increasing FCs, paid as a gradual reduction in virulence, competitiveness, and slow growth performance. Full article

Plant height is an important agronomic trait that affects the establishment of the ideal plant type and yield formation of rapeseed. However, the genetic mechanism affecting plant height has not been fully elucidated. Building on previous genome-wide association studies (GWASs), we performed differential gene expression analysis using 14 shoot apex transcriptome datasets derived from materials exhibiting extreme seedling height phenotypes at the bud stage. The promoter and the first exon regions of the Glycosylphosphatidylinositol 2 gene (BnGPI2-A03) of rapeseed were identified as harboring two significant SNPs (Bn-A03-p717776 and Bn-A03-p7178917) associated with plant height. Co-expression network analysis shows that BnGPI2-A03 was associated with many hormone pathway genes, cell wall synthesis pathway genes, and transcription factor genes and formed a potential network regulating the plant height of rapeseed. To examine the function of BnGPI2-A03 on plant height in Brassica napus L., we generated transgenic plants in which BnGPI2-A03 was overexpressed using a 35 s promoter. Overexpression of BnGPI2-A03 elevated the height and main inflorescence length of the transgenic plant by an average of 17.95% and 25.92%, respectively, which showed a positive relationship with the level of BnGPI2-A03. Transcriptome sequencing analysis of the overexpressed transgenic rapeseed stem-tip tissue during the bud stage shows that BnGPI2-A03 is associated with plant cell wall synthesis and cell division pathways. The requirement of BnGPI2-A03 for plant height was further evidenced in natural germplasms by the higher expression levels of BnGPI2-A03 in the stem-tip tissue of extremely high genotypes (Hap1) relative to their ultra-short counterparts (Hap3). These discoveries highlight potential targets for the plant height genetic improvement of rapeseed in the future. Full article

Background: Nephrogenic diabetes insipidus (NDI) is defined as the inability of the kidney to concentrate urine owing to the insensitivity of the distal nephron to the antidiuretic hormone, arginine vasopressin. NDI is a heterogeneous rare autosomal dominant or X-linked disease. Objective: We present a family with nephrogenic diabetes affecting three males in two generations. Methods: We report two boys with NDI: a 4-month-old infant who was treated for fever, vomiting, and failure to thrive, and his 10-year-old uncle (the mother’s brother), who was admitted concurrently for consuming 11 L of fluid per day. According to family history, the mother’s sibling passed away at the age of two from severe hypernatremic dehydration. Results: The infant’s clinical and laboratory evaluation revealed a 7.8 mL/kg/h urine output, hypernatremic hyperchloremic alkalosis, extremely low urine density (1002), and elevated copeptin level. In contrast, the uncle’s clinical and laboratory evaluation revealed marked polyuria, low urine density, and elevated copeptin, all of which were suggestive of diabetes insipidus. After starting hydrochlorothiazide treatment (2 mg/kg/body), the infant’s urine production reduced (2.85 mL/kg/h); however, severe hypokalemia and alkalosis followed. Spironolactone, an aldosterone antagonist, were added, with good therapeutic response. Hydrochlorothiazide was administered to the uncle, and his daily fluid intake decreased to 3–4 L. Given the family history, Sanger sequencing for the AVPR2 variant was performed on the boys and the infant’s mother. Analysis showed hemizygous likely pathogenic variant c.335G>A p. (Cys112Tyr) in the 2 boys and heterozygous (carrier) status of the mother. Within the same family, we observed phenotypic heterogeneity: one child died at the age of two, another lived well into ten years without therapy, and a four month-old baby could have had a poor outcome without specific treatment. Conclusions: NDI is a rare and possibly fatal genetic disorder with heterogeneous manifestations. In families with a history of NDI, molecular genetic testing is crucial for family planning. Full article

Background/Objectives: The first camelized mouse model (Nrap^c.255ins78) was developed to investigate the mechanisms underlying camels’ adaptation to extreme environments. Previous studies demonstrated that these mice exhibit a cold-resistant phenotype, characterized by increased expression of inflammatory cytokine-related genes in the heart under cold stress. Nebulin-related anchoring protein (NRAP) plays a critical role in organizing myofibrils during cardiomyocyte development. This study builds on prior research by analyzing the heart transcriptomes of Nrap^c.255ins78 mice under non-stress conditions to explore the origins of inflammatory cytokine responses during cold exposure. Methods: RNA sequencing was performed on the hearts of 12-week-old male and female Nrap^c.255ins78 and wild-type control mice. Results: Differential expression analysis identified 25 genes, including 12 associated with cell cycle and division, all consistently downregulated in Nrap^c.255ins78. Notably, the calcium and integrin-binding protein gene (Cib3) was significantly upregulated (FDR < 0.05; p < 0.001). Conclusions: These differentially expressed genes suggest altered calcium dynamics in cardiomyocytes and mechanisms for maintaining homeostasis, supporting the hypothesis that inflammatory cytokines during cold exposure may represent an adaptive response. These findings provide valuable insights into the genetic mechanisms of temperature adaptation in camels and highlight potential pathways for enhancing stress resistance in other mammals. Full article

Hadal zones account for the deepest 45% of oceanic depth range and play an important role in ocean biogeochemical cycles. As the least-explored aquatic habitat on earth, further investigation is still required to fully elucidate the microbial taxonomy, ecological significance, metabolic diversity, and adaptation in hadal environments. In this study, a novel strain Lsc_1132^T was isolated from sediment of the Mariana Trench at 10,954 m in depth. Strain Lsc_1132^T contains heterogenous 16S rRNA genes, exhibiting the highest sequence similarities to the type strains of Neobacillus drentensis LMG 21831^T, Neobacillus dielmonensis, Neobacillus drentensis NBRC 102427^T, Neobacillus rhizosphaerae, and Neobacillus soli NBRC 102451^T, with a range of 98.60–99.10% identity. The highest average nucleotide identity (ANI), the highest digital DNA-DNA hybridization (DDH) values, and the average amino acid identity (AAI) with Neobacillus sp. PS3-40 reached 73.5%, 21.4%, and 75.54%, respectively. The major cellular fatty acids of strain Lsc_1132^T included iso-C_15:0, Summed Feature 3 (C_16:1ω6c and/or C_16:1ω7c), iso-C_17:0, anteiso-C_15:0, and iso-C_17:1ω5c. The respiratory quinone of strains Lsc_1132^T was MK-7. The G + C content of the genomic DNA was 40.9%. Based on the GTDB taxonomy and phenotypic data, strain Lsc_1132^T could represent a novel species of a novel genus, proposed as Aliineobacillus hadale gen. nov. sp. nov. (type strain Lsc_1132^T = MCCC 1K09620^T). Metabolically, strain Lsc_1132^T demonstrates a robust carbohydrate metabolism with many strain-specific sugar transporters. It also has a remarkable capacity for metabolizing amino acids and carboxylic acids. Genomic analysis reveals a streamlined genome in the organism, characterized by a significant loss of orthologous genes, including those involved in cytochrome c synthesis, aromatic compound degradation, and polyhydroxybutyrate (PHB) synthesis, which suggests its adaptation to low oxygen levels and oligotrophic conditions through alternative metabolic pathways. In addition, the reduced number of paralogous genes in strain Lsc_1132^T, together with its high protein-coding gene density, may further contribute to streamlining its genome and enhancing its genomic efficiency. This research expands our knowledge of hadal microorganisms and their metabolic strategies for surviving in extreme deep-sea environments. Full article

Cardiomyopathy represents the most important life-limiting condition of Duchenne muscular dystrophy (DMD) patients after the age of 20. Genetic alterations in the DMD gene result in the absence of functional dystrophin protein, leading to skeletal/cardiac muscle impairment. The DMD incidence is one in 5000 live male births. Identifying the genetic background, in addition to DMD disease-causing variants, is one of the unmet needs in understanding the cardiac disease’s pathogenetic mechanisms and its prognostic implications. The clinical scenario is made even more intricate by the difficulty in predicting the onset and progression of cardiomyopathy, as no clear genotype/phenotype correspondence has been found thus far. The evaluation of genes involved in the onset of primary cardiomyopathies could explore the hypothesis that changes in cytoskeletal and sarcomeric protein function are the modulators of ventricular dysfunction in DMD patients. In the last decade, with the advent of next-generation sequencing (NGS) technology, many disease-causing genes and modifiers have been identified. Assessing the genetic origin of the phenotypic variability of the disease in both the onset and progression of cardiomyopathy in DMD would be extremely helpful in managing these patients. This review article aims to spotlight the genetic background associated with Cardiomyopathy in DMD patients toward a more predictive personalized model of care. Full article

Pathogenic KCNQ2 variants are associated with neonatal epilepsies, ranging from self-limited neonatal epilepsy to KCNQ2–developmental and epileptic encephalopathy (DEE). In this study, next-generation sequencing was performed, applying a panel of 142 epilepsy genes on three unrelated individuals and affected family members, showing a wide variability in the epileptic spectrum. The genetic analysis revealed two likely pathogenic missense variants (c.1378G>A and c.2251T>G) and the already-reported pathogenic splice site (c.1631+1G>A) in KCNQ2 (HGNC:6296). The phenotypes observed in the affected members of family 1, which shared the c.2251T>G variant, were epilepsy with auditory features (EAFs), focal epilepsy, and generalized epilepsy, and none of them suffered from neonatal seizures. The gene panel contained further genes related to EAFs (LGI1, RELN, SCN1A, and DEPDC5), which were tested with negative results. The phenotypes observed in family 2 members, sharing the splice site variant, were neonatal seizures and focal epilepsy in childhood. The last unrelated proband, harboring the de novo missense c.1378G>A, presented a clinical phenotype consistent with DEE. In conclusion, we identified two unreported KCNQ2 variants, and report a proband with EAFs and individuals without typical KCNQ2 neonatal seizures. Our study underscores the extreme variability in the phenotypic spectrum of KCNQ2-related epilepsies and unveils the prospect of its inclusion in screening panels for EAFs. Full article

Portuguese oyster (Magallana angulata) is one of the most important shellfish species worldwide. Although significant improvements in growth have been achieved through artificial selection breeding, the genetic basis underlying these traits remains unclear. Thus, this study aimed to (i) estimate variation and heritability for growth-related traits and (ii) identify SNPs and candidate genes associated with growth traits in Portuguese oyster. Five growth-related traits, including shell height (SH), shell length (SL), shell width (SW), whole weight (WW), and soft tissue weight (STW), were measured and analyzed in 114 one-year-old individuals from a cultivated population in Fujian Province, China. Through whole-genome sequencing and genotyping, we obtained 8,183,713 high-quality SNPs. Based on the genomic relationship matrix, heritability for the five traits was estimated, ranging from 0.071 to 0.695. Through genome-wide association analysis (GWAS), a total of nine SNPs were identified as significantly or suggestively associated with one of the growth-related traits, each explaining phenotypic variation ranging from 14.13% to 18.56%. Differentially expressed genes (DEGs) between individuals with extreme phenotypes were identified using comparative transcriptome analysis, ranging from 868 to 2274 for each trait. By combining GWAS and comparative transcriptome analysis, a total of seven candidate genes were identified, with biological functions related to growth inhibition, stress response, cell cycle regulation, and immune defense. The associations between the candidate genes and the growth-related traits were validated by using single-marker association analysis in other populations. Based on SNPs in these candidate genes, 16 haplotypes associated with growth-related traits were obtained. This study contributes to a deeper understanding of the genetic mechanisms of growth traits, and provides a theoretical basis and genetic markers for the breeding of fast-growing strains of the Portuguese oyster. Full article