Nuclear envelopathies are rare genetic diseases that compromise the integrity of the nuclear envelope. Patients with a defect in LEM domain nuclear envelope protein 2 (LEMD2) leading to LEMD2‐associated progeroid syndrome are exceedingly scarce in number, yet they exhibit shared clinical features including skeletal abnormalities and a prematurely‐aged appearance. Our study broadens the understanding of LEMD2‐associated progeroid syndrome by detailing its phenotypic and molecular characteristics in the first female and fourth reported case, highlighting a distinct impact on metabolic functions. The patient's history revealed growth delay, facial and skeletal abnormalities, and recurrent abdominal pain crises caused by hepatomegaly. Comparisons with the previously documented cases emphasized similarities in skeletal and facial features while showcasing unique variations, notably in cardiac and hepatic manifestations. In vitro experiments conducted on patient‐derived peripheral blood and urinary epithelial cells and LEMD2‐downregulated HepG2 cells confirmed abnormalities in the structure of the nuclear envelope in all three tissue‐types. Overall, our work offers a comprehensive profile of a patient with LEMD2‐related syndrome, emphasizing the hepatic involvement in the disease and broadening our understanding of clinical and molecular implications. This study not only contributes specific insights into LEMD2‐related conditions but also underscores potential therapeutic paths for disorders affecting nuclear envelope dynamics.

Citrin deficiency (CD) is an autosomal recessive disorder caused by the absence or dysfunction of the mitochondrial transporter citrin, resulting from mutations in SLC25A13. The disease presents with age‐dependent clinical manifestations: neonatal intrahepatic cholestasis caused by CD (NICCD), failure to thrive and dyslipidemia by CD (FTTDCD), and an adult‐onset form (formerly called Type II citrullinemia, CTLN2, recently renamed to “adolescent and adult citrin deficiency,” AACD). We performed this study to compile known genotypes found in CD patients and investigate their impact on the clinical course. Through a nationwide survey in Japan as well as a literature review, we collected information regarding 68 genetic variants of a total of 345 patients with CD (285 NICCD, 19 post‐NICCD, and 41 AACD). In this cohort, the pathogenic variants, arising from nonsense, insertion/deletion, and splice site mutations, are expected to have severe functional or biogenesis defects. Of 82 alleles in patients with AACD, the two most common variants, c.852_855del and c.1177+1G>A, accounted for 25 alleles (30.5%) and 15 alleles (18.3%), respectively. The c.852_855del variant, even when present as part of compound heterozygosity, often presented with hyperammonemia (≥ 180 μmol/L), cognitive impairment, short stature (< ‐2SD), liver cirrhosis, and pancreatitis, with some patients requiring liver transplantation. In conclusion, certain SLC25A13 genotypes are particularly frequent, especially those that result in severely truncated citrin proteins with often a significant impact on the clinical outcome of the patient. The most prevalent variant is c.852_855del, which was found in 42% (128/304) of NICCD/post‐NICCD cases and 49% (20/41) of AACD patients.

Modified Vaccinia virus Ankara (MVA) is a potent vector for the development of vaccines and novel cancer treatment strategies. Since it is a non‐replicating virus in human recipients, high infective titers are required for therapeutic efficacy. Harvesting and clarification of cell culture‐derived MVA are critical for the overall process yield and remains challenging, as full MVA release depends on cell lysis, resulting in a difficult‐to‐filter cell lysate. In this study, we present the development of a high‐yield clarification strategy using diatomaceous earth (DE) as a natural filter aid, followed by an optimized endonuclease treatment. An ionic strength containing a 650 mM salt mixture of NaCl, NaBr, and KCl allowed impurity depletion by DE binding while maintaining a complete virus recovery. The optimal alluvial filtration conditions were achieved with a PURAFIX® CH 09 depth filter with a 10–30 µm retention rate. The optimal conditions were identified as a combination of a Celpure® C1000 precoat and a Celpure® C300 additive added to the feed. This robust process achieved 94% total virus recovery while reducing turbidity to 23% and residual DNA and protein impurities to 76% and 72%, respectively, in a single‐step filtration. Subsequent nuclease digestion benefits from a reduced particle and impurity burden, resulting in further 93% DNA depletion under optimal conditions of 11 h of incubation at 21°C with 51 U/mL of the salt active DENARASE® High Salt endonuclease. The study demonstrated that sterilized filter aids enable a single‐step filtration to recover high MVA titers with a reduced impurity burden, paving the way for improved downstream process efficiency.