Search Results (64)

Background/Objectives: Infertility, defined as the failure to achieve pregnancy after one year of regular unprotected intercourse, represents a significant global health challenge, with male factors contributing to approximately 50% of cases. In this epidemiological context, both primary male infertility (the inability to conceive a first child) and secondary male infertility (which occurs when a man who has already fathered a child faces difficulty conceiving again) remain poorly understood at the genetic level. This study explored the role of single-nucleotide polymorphisms (SNPs) in mitochondrial genes (MT-ND3, MT-ND4L, and MT-ND4) in primary and secondary male infertility. Methods: This study analyzed the genotype distributions of SNPs in 68 infertile males (49 with primary infertility and 19 with secondary infertility) using Sanger sequencing. Results: Key findings revealed that studied SNPs were significantly associated with infertility type. Specifically, rs2857285 (T>C,G) in the ND4 gene showed a significant correlation (p = 0.023) with the TT genotype, which is prominent in primary infertility. Another SNP, rs28358279 (T>A,C) in the ND4L gene, also demonstrated a significant correlation (p = 0.046) with the TT genotype, being more common in primary infertility. In addition, rs869096886 (A>G) in the ND4 gene had a borderline correlation (p = 0.051), indicating a possible association between this SNP and reproductive duration. Conclusions: This study emphasizes the potential relevance of mitochondrial malfunction in male infertility, specifically the effects of studied SNPs on sperm survival and function over time. These findings suggest that certain mitochondrial SNPs might be potential biomarkers for infertility risk. Larger studies are needed to confirm these associations and examine the functional effects of these SNPs. Combining genetic analysis with environmental and lifestyle factors could enhance our understanding of male infertility and improve diagnostic and therapeutic strategies. Full article

This study investigates the complex relationship between levels of religiosity and attitudes toward secularization among individuals receiving higher religious education in Türkiye. Secularization is defined as the diminishing influence of religion in public life and the rise of critical attitudes toward religious norms, a process that accelerated particularly during the modernization period following the establishment of the Republic. The primary aim of the research is to analyze whether there is a significant relationship between secular attitudes and the perceived influence of Islam among theology faculty students. The study employs a quantitative, descriptive survey design and includes a sample of 380 undergraduate, graduate, and doctoral students from the faculties of theology at Kocaeli, Sakarya, Marmara, and Istanbul universities. Data were collected using the “Perceived Influence of Religion Scale” and the “Secular Attitude Scale,” both of which demonstrated acceptable reliability (Cronbach’s Alpha = 0.70). Demographic variables such as age, gender, marital status, parental education level, type of education (formal or distance), and economic status were also incorporated into the analysis. The findings revealed statistically significant differences based on marital status, parental education level, type of education program, and previous educational background. For instance, single students reported perceiving a higher influence of religion compared to their married counterparts, while students with fathers who held university degrees perceived a lower influence of religion. These results offer valuable insights into how modern social transformations influence religious attitudes and practices. Full article

Background: Caregivers in urban settings often face unique challenges in providing nurturing care. This qualitative study explores the complex realities of caregiving among mothers and grandmothers in urban poor neighbourhoods of Bangalore, South India. Grounded in Bronfenbrenner’s ecological systems theory, this is the first study in urban India that examines how caregivers’ perceptions, along with individual and systemic factors, shape caregiving practices in this setting. Methods: In-depth interviews (IDIs) were conducted with 22 mothers and grandmothers of 4–6-year-old children from the urban MAASTHI cohort in Bangalore, South India. Topic guides were developed, pre-tested, and piloted. IDIs were conducted in local languages (Kannada and Hindi). Transcripts were coded using NVivo 12 plus and analyzed via a thematic analysis approach using Bronfenbrenner’s ecological systems framework to organize themes. Findings: At the microsystem level, caregivers engaged with children through storytelling and play, though competing demands like household chores often constrained these interactions. Disciplining techniques varied, and the absence of fathers placed additional burdens on mothers. The mesosystem revealed the critical role of extended family in providing support. At the exosystem level, unsafe neighbourhoods limited children’s opportunities for outdoor play. The macrosystem highlighted how religious values provided moral frameworks for parenting and the presence of stigma against single mothers. The chronosystem explored declining social support over time and challenges. Conclusions: These findings emphasize that caregiving inequities are not isolated but structurally embedded, demanding interventions that address sociocultural, economic, and spatial barriers to equitable support for caregivers, particularly those in disadvantaged settings. It calls for context-sensitive interventions, including community-based parenting programmes including maternal well-being, strengthening community and public support systems, improving safe play spaces, and longitudinal research. By amplifying marginalized caregivers’ voices, this research highlights the need for policies that support nurturing care in low-resource settings to break intergenerational cycles of disadvantage. Full article

Background/Objectives: Chronic pancreatitis (CP) is a progressive inflammatory condition of the pancreas that leads to irreversible changes in pancreatic structure. The pancreatic α and β cells secrete hormones such as insulin and glucagon into the bloodstream. The pancreatic acinar cells secrete digestive enzymes that break down macromolecules. When these digestive enzymes do not function properly, maldigestion, malabsorption, and malnutrition may result. Presented here is a case study of an individual newly diagnosed with chronic pancreatitis, along with a genetic analysis of his son and an in-silico analysis of two of the variant proteins. Methods: This study was conducted using human subjects, namely, the proband (father) and his son. Medical genetic testing of the proband (father) identified the presence of two variants in the cystic fibrosis transmembrane receptor gene (CFTR): variant rs213950, resulting in a single amino acid change (p. Val470Met), and variant rs74767530, a nonsense variant (Arg1162Ter) with known pathogenicity for cystic fibrosis. Medical testing also revealed an additional missense variant, rs515726209 (Ala73Thr), in the CTRC gene. Cheek cell DNA was collected from both the proband and his son to determine the inheritance pattern and identify any additional variants. A variant in the human leukocyte antigen (rs7454108), which results in the HLA-DQ8 haplotype, was examined in both the proband and his son due to its known association with autoimmune disease, a condition also linked to chronic pancreatitis. In silico tools were subsequently used to examine the impact of the identified variants on protein function. Results: Heterozygosity for all variants originally identified through medical genetic testing was confirmed in the proband and was absent in the son. Both the proband and his son were found to have the DRB1*0301 (common) haplotype for the HLA locus. However, the proband was also found to carry a linked noncoding variant, rs2647088, which was absent in the son. In silico analysis of variant rs213950 (Val470Met) in CFTR and rs515726209 (Ala73Thr) in CTRC revealed distinct changes in predicted ligand binding for both proteins, which may affect protein function and contribute to the development of CP. Conclusions: This case study of a proband and his son provides additional evidence for a polygenic inheritance pattern in CP. The results also highlight new information on the role of the variants on protein function, suggesting additional testing of ligand binding for these variants should be done to confirm the functional impairments. Full article

One out of every hundred live births present with congenital heart abnormalities caused by the aberrant development of the embryonic cardiovascular system. The conserved zinc finger transcription factor proteins, which include GATA binding protein 5 (GATA5) and GATA binding protein (GATA6) play important roles in embryonic development and their inactivation may result in congenital heart defects (CHDs). In this study, we performed genotypic–phenotypic analyses in two families affected by right-sided CHD diagnosed by echocardiography imaging. Proband A presented with pulmonary valve stenosis, and proband B presented with complex CHD involving the right heart structures. For variant detection, we employed whole-genome single-nucleotide polymorphism (SNP) microarray and family-based whole-exome sequencing (WES) studies. Proband A is a full-term infant who was admitted to the neonatal intensive care unit (NICU) at five days of life for pulmonary valve stenosis (PVS). Genomic studies revealed a normal SNP microarray; however, quad WES analysis identified a novel heterozygous [Chr20:g.61041597C>G (p.Arg237Pro)] variant in the GATA5 gene. Further analysis confirmed that the novel variant was inherited from the mother but was absent in the father and the maternal uncle with a history of heart murmur. Proband B was born prematurely at 35 weeks gestation with a prenatally diagnosed complex CHD. A postnatal evaluation revealed right-sided heart defects including pulmonary atresia with intact ventricular septum (PA/IVS), right ventricular hypoplasia, tricuspid valve hypoplasia, hypoplastic main and bilateral branch pulmonary arteries, and possible coronary sinusoids. Cardiac catheterization yielded anatomy and hemodynamics unfavorable to repair. Hence, heart transplantation was indicated. Upon genomic testing, a normal SNP microarray was observed, while trio WES analysis identified a novel heterozygous [Chr18:c.1757C>T (p.Pro586Leu)] variant in the GATA6 gene. This variant was inherited from the father, who carries a clinical diagnosis of tetralogy of Fallot. These findings provide new insights into novel GATA5/6 variants, elaborate on the genotypic and phenotypic association, and highlight the critical role of GATA5 and GATA6 transcription factors in a wide spectrum of right-sided CHDs. Full article

Residents of Bangladesh are exposed to numerous chemicals due to local industries, including dyeing mills, cotton mills, and the use of biomass in daily cooking. It is, therefore, important to characterize the exposome and work to identify risk factors of exposure. We used silicone wristband passive samplers to evaluate exposure to volatile and semi-volatile organic compounds in a sample of 40 children in the Araihazar upazila of Bangladesh. We used stepwise linear regression models to determine which demographic, exposure, diet, and socioeconomic factors best predict exposure to single chemicals and classes of chemicals. Male sex at birth was associated with a decrease in the number of chemicals detected above their median concentration (β = −2.42; 95%CI: −5.24, 0.399), as was ownership of a flush toilet (β = −3.26; 95%CI: −6.61, 0.097). Increased body mass index (β = 1.81; 95%CI: 0.587, 3.03), father’s smoking (β = 2.74; 95%CI: −0.0113, 5.49), and father’s employment in the garment industry (β = 3.14; 95%CI: 0.209, 6.07) were each associated with an increase in the average number of chemicals detected above their median concentration. The observed results motivate future evaluation with health outcomes of these exposures. Full article

Background: Childhood obesity is a significant public health issue. This study aimed to evaluate the prevalence of overweight and obesity among 8- and 9-year-old children in Szczecin, Poland, and unlike other studies to assess differences in nutritional status within a single urban agglomeration of nearly 500,000 residents, it was influenced by place of residence and socioeconomic status. Methods: The study included 4705 children (2327 boys and 2378 girls) aged 8 and 9 years, attending 50 primary schools in Szczecin (45 public, 5 private) across four districts: North, Right Bank, City Center, and West. Anthropometric measurements were used to calculate BMI. Overweight was diagnosed when BMI was ≥85th percentile but lower than the 95th percentile for age and sex, while obesity was when the BMI was ≥95th percentile. Data on parental BMI, education, and place of residence were also collected. Results: The prevalence of overweight was 16.6%, and obesity was 6.2%. Overweight was more common in girls, while obesity was more frequent in boys. Children attending special education schools and living in the Right-Bank district had the highest rates of overweight and obesity. Parental obesity and low parental education, particularly the father’s, were the strongest risk factors for excess body weight. Conclusions: Differences in childhood nutritional status exist even within the same city, influenced by residence and socioeconomic factors. Parental obesity, low education, living in the city’s rural districts, and attending special education schools are key risk factors. Enhanced prevention programs tailored to these factors are crucial to combat childhood obesity effectively. Full article

Background/Objectives: Adolescence is an important period of psychophysical development. In this phase of life people acquire greater self-awareness and adopt behaviors that will later shape their lifestyle in adulthood. This study aimed to assess whether family structure can influence adolescents’ eating habits. Methods: Data were acquired from a survey titled ‘Italian Health Behaviour in School-aged Children’ (HBSC) given to a representative sample of Tuscan adolescents aged 11, 13, 15 and 17 years of age. Participants (3210) filled out a validated questionnaire answering questions about their eating habits and family structure. After adjusting for covariates, some interesting trends were highlighted in the survey results. Results: Adolescents living in single-mother families reported a lower intake of fruits (OR 0.68, 95% CI = 0.55–0.83) and vegetables (OR 0.66, 95% CI = 0.53–0.81) and a higher intake of sugar-added soft drinks (OR 1.33, 95% CI = 1.08–1.64). Living in a mother and stepfather family was associated with a higher intake of sugar-added soft drinks (OR 1.53, 95% CI = 1.02–2.28), whereas living in a father and stepmother family was associated only with a lower intake of fruits (OR 0.48, 95% CI = 0.26–0.87). Participants living with other family types reported a lower intake of vegetables (OR 0.68, 95% CI = 0.47–0.98). Conclusions: The results of this study show a correlation between family structure and adolescents’ eating habits. Full article

Disorders of sexual development (DSDs) in dogs, similar to humans, arise from genetic mutations, gonadal differentiation, or phenotypic sex development. The French Bulldog, a breed that has seen a surge in popularity and demand, has also shown a marked increase in DSD incidence. This study aims to characterize the genetic underpinnings of DSDs in a French Bulldog named Brutus, exhibiting ambiguous genitalia and internal sexual anatomy, and to explore the impact of breeding practices on genetic diversity within the breed. We utilized a comprehensive approach combining conventional cytogenetics, molecular techniques, and deep sequencing to investigate the genetic profile of Brutus. The sequence data were compared to three other male French Bulldogs’ genome sequences with typical reproductive anatomy, including Brutus’s father and the canine reference genome (CanFam6). We found a Robertsonian fusion involving chromosome 23 previously reported in dogs as a causative mutation responsible for sex reversal syndrome. Our findings revealed a 22% mosaicism (78,XX/77,XX), the absence of the sex-determining region (SRY) gene, and the presence of 43 unique Single Nucleotide Variants (SNVs) not inherited from the father. Notably, the run of homozygosity (ROH) analysis showed Brutus has a higher number of homozygous segments compared to other Bulldogs, with a total length of these fragments 50% greater than the average, strongly suggesting this dog is the product of the mating between siblings. Although no direct causative genes for the DSD phenotype were identified, four candidate loci warrant further investigation. Our study highlighted the need for a better annotated and curated reference dog genome to define genes causative of any specific phenotype, suggests a potential genetic basis for the DSD phenotype in dogs, and underscores the consequences of uncontrolled breeding practices in French Bulldogs. These findings highlight the importance of implementing strategic genetic management to preserve genetic health and diversity in canine populations. Full article

A 16-year-old patient, while an infant, incurred right-sided hemiparesis and had difficulty breast feeding. She was later diagnosed with a neonatal stroke and her genetic testing showed a missense mutation in her PROS1 (Protein S) gene. Both her grandfather and father, but not her mother, had hereditary Protein S (PS) deficiency. The patient was not prescribed any mediation due to her young age but was frequently checked by her physician. The patient’s plasma was first collected at the age of 13, and the isolated plasma from the patient and her father were analyzed by aPTT, thrombin generation, and enzyme-linked immunosorbent assays. These analyses showed low PS activity and clotting time associated with the missense mutation in the PROS1 gene. During the COVID-19 pandemic, the patient received her first Pfizer vaccination dose in 2021, followed by a booster dose in 2022. The plasma samples were collected 8 weeks post-immunization, after which her clotting parameters had improved for up to 6 months following vaccination. The patient’s plasma showed a significant reduction in thrombin generation and an improved aPTT clotting time. Mass spectrometry analysis revealed that her antithrombin-III level was significantly higher post-vaccination, and both thrombin and FXII levels were significantly lowered compared with her father. To our knowledge, this is the first report to document that COVID-19 vaccination can lower the risk of thrombosis in a patient with inherited thrombophilia. Although the effect was observed on a single mutation, it would be interesting to investigate the effect of COVID-19 vaccinations on other thrombophilia. Full article

Waardenburg syndrome (WS) is a common genetic cause of syndromic hearing loss, accounting for 2–5% of congenital cases. It is characterized by hearing impairment and pigmentation abnormalities in the skin, hair, and eyes. Seven genes are associated with WS: PAX3, MITF, EDNRB, EDN3, SOX10, KITLG, and SNAI2. This study investigates the genetic causes of WS in three familial cases. Whole-exome sequencing (WES) was performed to identify single nucleotide variants (SNVs). Copy number variants (CNVs) were analyzed from the WES raw data and through multiplex ligation-dependent probe amplification (MLPA). The study identified one pathogenic SNV and two novel CNVs, corresponding to type I and type II WS patterns in the three families. The SNV, a nonsense variant (c.1198C>T p.Arg400*), was found in MITF and segregated in the affected father. The two CNVs were a deletion of exon 5 in PAX3 in a family with two affected members and a large novel deletion comprising seven genes, including SOX10, in a family with three affected members. These findings confirmed a WS diagnosis through genetic testing. The study emphasizes the importance of integrating multiple genetic testing approaches for accurate and reliable diagnosis, highlighting their role in improving patient management and providing tailored genetic counseling. Full article

A genetic diagnosis of primary cardiomyopathies can be a long-unmet need in patients with complex phenotypes. We investigated a three-generation family with cardiomyopathy and various extracardiac abnormalities that had long sought a precise diagnosis. The 41-year-old proband had hypertrophic cardiomyopathy (HCM), left ventricular noncompaction, myocardial fibrosis, arrhythmias, and a short stature. His sister showed HCM, myocardial hypertrabeculation and fibrosis, sensorineural deafness, and congenital genitourinary malformations. Their father had left ventricular hypertrophy (LVH). The proband’s eldest daughter demonstrated developmental delay and seizures. We performed a clinical examination and whole-exome sequencing for all available family members. All patients with HCM/LVH shared a c.4411-2A>C variant in ALPK3, a recently known HCM-causative gene. Functional studies confirmed that this variant alters ALPK3 canonical splicing. Due to extracardiac symptoms in the female patients, we continued the search and found two additional single-gene disorders. The proband’s sister had a p.Trp329Gly missense in GATA3, linked to hypoparathyroidism, sensorineural deafness, and renal dysplasia; his daughter had a p.Ser251del in WDR45, associated with beta-propeller protein-associated neurodegeneration. This unique case of three monogenic disorders in one family shows how a comprehensive approach with thorough phenotyping and extensive genetic testing of all symptomatic individuals provides precise diagnoses and appropriate follow-up, embodying the concept of personalized medicine. We also present the first example of a splicing functional study for ALPK3 and describe the genotype–phenotype correlations in cardiomyopathy. Full article

The mutation HBA2:c.*94A>G (AATAAA>AATAAG; rs63751269) is a 3′-UTR (3 prime untranslated region) single-nucleotide substitution in the polyadenylation (PA) signal of HBA2 (α^PA:A→G). This pathogenic (CADD score, 14.92) variant is sporadic in the Arabian Peninsula. It results in inefficient mRNA processing, transcription termination, and possibly using an alternate cryptic downstream polyadenylation signal. As a result, the allele α^T (or α^T-Saudi) poses challenges in premarital counseling with respect to fetal risk of hemoglobin H disease. Homozygous HBA2:c.*94A>G (α^Tα/α^Tα) results in moderate-to-severe microcytosis (mean red cell volume, MCV, 55 to 65 fL), reflecting markedly impaired hemoglobin synthesis (hemoglobin H disease). Homozygous rightward −α^3.7 (a 3804-neocleotide deletion allele, NM_000517.4:c.[-2_-3delAC; −α^3.7]), on the other hand, results in mild microcytosis (MCV, 70 to 75 fL, alpha-thalassemia trait). Thus, HBA2:c.*94A>G is more damaging than −α^3.7. Consistently, the value of MCV in compound heterozygosity, HBA2:c.*94A>G and −α^3.7, is 65 to 70 fL. We report here a healthy couple who presented for premarital counseling on their hemoglobinopathy. The man has homozygous HBA2:c.*94A>G (α^Tα/α^Tα), and the woman has compound heterozygous (−α^3.7/α^Tα, also annotated as: ^−3.7α/α^Tα). As a result, the genotype of their offspring would be that of the father (α^Tα/α^Tα) or the mother (−α^3.7/α^Tα). The counseling was mainly based on the benign phenotypes of the parents. As both were asymptomatic and their anemia was clinically insignificant, they proceeded with the marriage. Full article

Even though it is already known that parents of children with developmental delays or disabilities experience higher parenting stress than families of typically developing children, the contributing factors need to be analyzed in more detail. The aim of this cross-sectional study was to examine the influence of demographic characteristics on parenting stress from caring for a disabled child and to identify possible protective or additional stressful social factors. A total of 611 mothers and fathers of children with developmental delays, chronic diseases, or disabilities completed two questionnaires during their medical appointments at the Children’s Development Center (CDC) of Leipzig University Hospital between June 2020 and February 2021. These consisted of the German versions of the Parenting Stress Index (PSI) and the Impact on Family Scale (IOFS). To determine differences between the various groups, we used parametric and non-parametric tests. Mothers and single parents are significantly more strained than fathers and non-single parents. Parents with vocational training, those who graduated with a higher-level diploma, and those within employment report a higher financial burden. While unemployed and full-time workers experience the lowest stress, parents who work part-time or exclusively take care of their child show higher levels of stress. Looking at the age of the child, parents of children of young primary school age are the most stressed, and those of infants are the least stressed. These findings suggest that mothers and single parents especially should receive more support, and parents need to be provided with more attention during their child’s entry into school. Possible limitations and the influence of the COVID-19 pandemic are discussed. Full article

Recently, we described the alteration of six miRNAs in the serum of autistic children, their fathers, mothers, siblings, and in the sperm of autistic mouse models. Studies in model organisms suggest that noncoding RNAs participate in transcriptional modulation pathways. Using mice, approaches to alter the amount of RNA in fertilized eggs enable in vivo intervention at an early stage of development. Noncoding RNAs are very numerous in spermatozoa. Our study addresses a fundamental question: can the transfer of RNA content from sperm to eggs result in changes in phenotypic traits, such as autism? To explore this, we used sperm RNA from a normal father but with autistic children to create mouse models for autism. Here, we induced, in a single step by microinjecting sperm RNA into fertilized mouse eggs, a transcriptional alteration with the transformation in adults of glial cells into cells affected by astrogliosis and microgliosis developing deficiency disorders of the ‘autism-like’ type in mice born following these manipulations. Human sperm RNA alters gene expression in mice, and validates the possibility of non-Mendelian inheritance in autism. Full article