Current Issue : October-December Volume : 2026 Issue Number : 4 Articles : 6 Articles
This cross-sectional online survey study explores the landscape of medical training on genetic therapies, assessing the experience, expectations and attitudes of medical geneticists, other specialists, and medical trainees in Canada and USA. Among the 315 participants, only 17% reported being “very familiar” with genetic therapies, and 70% expressed dissatisfaction with current training in this area. Across all groups, there was a consistently low level of satisfaction with existing training on genetic therapies, coupled with a strong consensus that this topic should be better integrated into medical programs. Physicians with specialization in genetics reported the highest familiarity and the most experience in teaching about genetic therapies, covering a broader range of topics than other specialties. All specialties acknowledged the pivotal role of medical geneticists in advancing education on genetic therapies. Instead of each specialty designing their own fellowship programs independently, there was a clear preference to do so in collaboration with medical geneticists. Furthermore, most respondents advocated for the introduction of genetic therapy education earlier in medical training, during medical school and residency programs. Our study highlights a clear and pressing need for comprehensive, stage-specific education reform about genetic therapies. Medical geneticists are uniquely positioned to lead and support these educational efforts, ensuring the successful adoption of advanced genetic therapies in patient care....
Background: The correlation between renal volume (or mass) and nephron number in newborns allows the use of the total kidney volume (TKV) at birth as a surrogate for congenital nephron number. Previously, the wide variation in final nephron number (termed “nephron endowment”) has been attributed to polymorphisms of genes encoding proteins involved in glomerulogenesis, including key genetic variants in the renin–angiotensin system. However, there are no data concerning the role of polymorphism in the gene encoding type-2 angiotensin II receptor (AGTR2) in the modulation of nephron endowment in humans. Therefore, the aim of our study was to analyze the possible association between AGTR2:rs1403543 polymorphism and kidney volume in Polish full-term healthy newborns. Methods: The study group consisted of 208 healthy, Polish, full-term newborns born to healthy women with uncomplicated pregnancies. The AGTR2:rs1403543 polymorphism was identified by PCR-RFLP in genomic DNA extracted from cord blood leukocytes. Kidney volume was measured sonographically. Total kidney volume was calculated as the sum of left and right kidneys, and normalized for body mass (BM), body length (BL), or body surface area (BSA). Results: There were no significant differences in TKV/BM, TKV/BL, or TKV/BSA between male and female newborns, as well as in regard to the AGTR2:rs1403543 polymorphism. Conclusions: The results suggest a lack of association between the AGTR2:rs1403543 polymorphism and physiological variability in kidney volume in full-term newborns....
Background/Objectives: DDX3X syndrome (MIM#300958) is a neurodevelopmental disorder associated with intellectual disability, language impairment, and a characteristic neurobehavioral phenotype that predominantly affects females. Although dysmorphic features have been reported, a consistent facial phenotype and clear genotype–phenotype correlations have not been established. Methods: We conducted an observational, ambispective, descriptive study including patients aged 0–18 years with a molecular diagnosis of DDX3X. Clinical, standardized facial images, neurobehavioral, neuroimaging, and molecular data were collected. Automated facial analysis was performed using Face2Gene after algorithm training. Results: Of 11 identified patients, 9 were included (8 females); 8 variants were de novo and 4 novel. Two variants of uncertain significance underwent in silico analysis. Frequent facial features included thin upper lip (9/9), tapered chin (8/9), long uniform eyebrows (8/9), short neck (8/9), and long face (6/9). After training, Face2Gene identified DDX3X syndrome in 92% of cases within the top 5 suggestions, supporting its utility as a diagnostic aid. All females had intellectual disability and language disorder; 66% presented sleep disturbances and aggressive behavior. Neuroimaging revealed ventricular dilatation (5/9) and corpus callosum hypoplasia (3/9). Loss-of-function variants were associated with greater clinical severity. Conclusions: This series suggests a recognizable facial phenotype of DDX3X syndrome and supports a possible genotype–phenotype correlation. Further studies are needed to confirm these findings....
We evaluated how much cardiorespiratory fitness (CRF)- related genetics contribute to the risk of common noncommunicable diseases (NCDs) and mortality, and whether individuals with different levels of CRF and genetic predispositions differ in health characteristics. We used a validated SBayesR- based genome- wide polygenic score, leveraging information from 905 707 single- nucleotide polymorphisms, to measure CRF genetics (PGS CRF). Associations with register- based incident NCDs and mortality were analyzed using Cox proportional hazards models in the FinnGen cohort (N = 262 137; 53.5- years at baseline, 52.0% women) and replicated in the HUNT3 cohort (N = 26 115; 59.0- years, 52.4% women). In HUNT3, we also compared the health characteristics of individuals having age- and sex- specific high or low CRF (V̇O2peak), and high or low PGS CRF (N = 1316). PGS CRF was negatively associated with any CVD (hazard ratio [HR] 0.99, 95% confidence interval 0.98–1.00), ischemic heart diseases (HR 0.98, 0.97–0.99), hypertensive diseases (HR 0.99, 0.97–1.00), stroke (HR 0.98, 0.97–1.00), lung cancer (HR 0.95, 0.92–0.97), chronic lower respiratory disease (HR 0.98, 0.97–0.99), chronic obstructive pulmonary disease (HR 0.97, 0.95–0.99), type 2 diabetes (T2D) (HR 0.96, 0.95–0.97), and all- cause mortality (HR 0.98, 0.97–0.99), per each standard deviation increase in PGS. Replication analyses supported the association with T2D. No differences in health characteristics were observed by genetic predisposition to CRF, while those with high V̇O2peak had a healthier profile in comparison to those with low V̇O2peak. The genome- wide PGS explains only a fraction of the CRF phenotype, yet some small associations were observed, particularly for T2D incidence....
This study reports a previously unreported heterozygous MYCN missense variant, c.454G>A (p.Ala152Thr), identified in a child and two affected relatives, with clinical findings consistent with Feingold syndrome type 1, an autosomal dominant developmental disorder most commonly caused by loss-of-function variants in MYCN. The proband presented with a cleft palate, craniofacial dysmorphism, feeding difficulties, hypotonia, and characteristic digital anomalies. Similar features were observed in the father and sibling. Clinical exome sequencing revealed the novel MYCN variant, which was confirmed by Sanger sequencing and demonstrated co-segregation with the phenotype. Although most pathogenic MYCN variants leading to FS1 truncate the protein, this missense change lies within the N-terminal transactivation domain, a region involved in transcriptional regulation and protein stability. The physicochemical alteration introduced at residue Ala152 may plausibly affect MYCN function, consistent with haploinsufficiency as the established disease mechanism. According to the 2024 ACGS Best Practice Guidelines, the variant was classified as a variant of uncertain significance leaning toward pathogenicity. This report expands the mutational spectrum of MYCN, supports the potential clinical relevance of N-terminal missense variation in MYCN, and highlights intrafamilial phenotypic variability in FS1....
Background/Objectives: Opioid use disorder (OUD) is caused by a complex interplay between genetic and non-genetic factors. DNA methylation is an epigenetic mechanism that modulates gene expression. Data on DNA methylation and opioid addiction and treatment are limited. This association study was designed to assess the difference in genomewide methylation patterns between individuals with OUD in methadone maintenance treatment (MMT) (n = 114) and those with OUD who achieved long-term abstinence (>10 years) without mu opioid receptor agonist treatment (n = 136). Methods: Differential DNA methylation analysis was performed in whole blood using the Illumina EPIC array. Results: A total of 135 differentially methylated probes (DMPs) reached epigenome-wide significance (p < 1 × 10−7), controlling for sex, age, estimates of blood cell proportions, and the first two principal components based on genome-wide SNP genotypes. The methylation sites were annotated to 157 genes, including 32% long non-coding RNAs. These genes are related to several systems, including cell adhesion (e.g., SAXO4), immune system and inflammation (e.g., UBTF, USP39, C10orf90, PRKCA), stress response (e.g., CRHR1, GPR19), and spermatogenesis (e.g., SPATA16, COX7B2). DMP cg11641410 is located in lncRNA ENSG00000254687, an antisense to OPRK1. Six of the DMPs were also identified in a related longitudinal study of MMT. Conclusions: At this point, it is not possible to determine whether the minor methylation differences observed in this study cause clinically relevant changes in gene expression. However, these findings have the potential to identify biomarkers and to provide new targets for treatment optimization....
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