Characterization and Analysis of PHEX Variants in Patients With Hypophosphatemia in Argentina.

Targeted next-generation sequencing in the molecular diagnosis of hereditary hemochromatosis

Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism characterized by excessive iron accumulation and considerable phenotypic variability, often making diagnosis challenging. This study aimed to identify pathogenic variants associated with HH using targeted next-generation sequencing (NGS). In addition, we investigated rare and novel genetic variants to improve diagnostic accuracy and support more personalized patient management strategies. A targeted NGS panel encompassing 12 genes involved in HH and iron homeostasis was applied. Variant interpretation followed the American College of Medical Genetics and Genomics (ACMG) guidelines, with all findings confirmed by PCR–Sanger sequencing. Structural analyses were conducted exclusively for variants of uncertain significance (VUS) using AlphaFold3 and visualized in PyMOL. Pathogenic variants were detected, notably the established HJV- p.Gly320Val variant, supporting a diagnosis of juvenile HH. An ultra-rare variant of uncertain significance, ERFE -c.478G > A (p.Ala160Thr), was also identified, with structural modeling indicating potential alterations that could affect protein function. Additionally, the established SLC40A1 -p.Arg178Gln variant was detected in a control sample, validating the robustness of the methodology. Overall, these results highlight the utility of targeted NGS and structural modeling in improving diagnostic accuracy and enabling precision medicine approaches in HH.

Clinical and genetic characterization of X-linked agammaglobulinemia in a Colombian cohort

Introduction X-linked Agammaglobulinemia (XLA) is an inborn error of immunity (IEI) caused by mutations in the BTK gene, resulting in the absence of mature B-cells and altered serum immunoglobulin levels. In Colombia, unified epidemiological and genetic data are lacking. This study aims to characterize XLA patients in the country demographically, phenotypically, and genotypically. Methods A multicenter, observational, cross-sectional study based on clinical records. Thirty-eight patients with B-cell counts <2% and hypogammaglobulinemia were included. Clinical, immunological, and genetic variables and outcomes were analyzed using descriptive statistics in R-Studio. Results Thirty-eight males were analyzed, with a median age at diagnosis of 16 months (IQR 7.2–21.8). Genetic testing was available for 84.2% (n = 32), identifying 15 distinct variants, 53% of which were novel. Sinopulmonary infections were the primary manifestation (92.1%), notably pneumonia (42.1%) and otitis media (39.5%). Median baseline IgG levels were 187 mg/dL. Bronchiectasis was documented in 34.2% of cases. The eight-year survival rate was 71.1%. Discussion The Colombian cohort shows a relatively early diagnosis but a high burden of structural sequelae (bronchiectasis), suggesting a need to optimize immunoglobulin replacement therapy. The high proportion of novel genetic variants underscores the importance of regional studies. This study represents the most robust characterization of XLA in Colombia, providing key data to improve clinical suspicion and prognosis.

Two variants in SLC34A3 in a patient with X-linked hypophosphatemia: a diagnostic and therapeutic dilemma.

[Clinical manifestation and analysis of FBN1 gene variants in eight patients with Marfan syndrome].

Findings have enriched the mutational spectrum of the FBN1 gene among Chinese MFS patients and provided a basis for the genetic counseling and clinical management.

[Clinical characterization and genetic analysis of a patient with Fahr disease due to a homozygous variant of JAM2 gene].

The patient had developed unsteady gait 6 months before without clear cause, manifesting as a feeling of heaviness in the head and lightness in the feet, a sensation of walking on cotton wool when standing or walking, and the detection of the novel variant has enriched the mutational spectrum of the JAM2 gene.

[Clinical and genetic characteristics and genotype-phenotype correlations of pheochromocytoma and paraganglioma in children and adolescents].

PPGL in children and adolescents presents a strong hereditary predisposition; SDHB and VHL germline variants lead to distinctly divergent clinical phenotypes.