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UBA1 is an E1 ubiquitin-activating enzyme that initiates the ubiquitylation of target proteins and is thus a key component of the ubiquitin signaling pathway. Three disorders are associated with pathogenic variants of the UBA1 gene: vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome, lung cancer in never smokers (LCINS), and X-linked spinal muscular atrophy (XL-SMA, SMAX2). We here report a case of infantile respiratory distress syndrome followed by continuing neuromuscular symptoms. We identified a de novo hemizygous mutation, c.1660 C > T (p.Pro554Ser), in exon 15 of the UBA1 gene in this baby. This missense mutation was located with the AAD (active adenylation domain) of the protein, a known hotspot of SMAX2 mutations. This case lends support to the genotype-phenotype correlation regarding the UBA1 mutation and its related diseases. [ABSTRACT FROM AUTHOR]

Background: Few studies have compared the efficacy and complications of dexmedetomidine (DEX) and fentanyl (FEN) in extremely preterm infants. Methods: We conducted a single‐institution, retrospective controlled before and after study of preterm infants before 28 weeks of gestation admitted between April 2010 and December 2018 to compare the complications and efficacy of DEX and FEN for preterm infants. Patients were administered FEN prior to 2015 and DEX after 2015 as the first‐line sedative. A composite outcome of death during hospitalization and developmental quotient (DQ) < 70 at a corrected age of 3 years was compared as the primary outcome. Secondary outcomes including postmenstrual weeks at extubation, days of age when full enteral feeding was achieved and additional sedation by phenobarbital (PB) were compared. Results: Sixty‐six infants were enrolled into the study. The only perinatal factor that differed between the FEN (n = 33) and DEX (n = 33) groups was weeks of gestation. The composite outcome of death and DQ < 70 at a corrected age of 3 years were not significantly different. Postmenstrual weeks at extubation did not significantly differ between groups after adjustment for weeks of gestation and being small for gestational age. On the other hand, full feeding was significantly prolonged by DEX (p = 0.031). Additional sedation was less common in the DEX group (p = 0.044). Conclusion: The composite outcome of death and DQ < 70 at a corrected age of 3 years were not significantly different by DEX or FEN for primary sedation. Prospective randomized controlled trials should examine the long‐term effects on development. [ABSTRACT FROM AUTHOR]

GATA4 is known to be a causative gene for congenital heart disease, but has also now been associated with disorders of sexual development (DSD). We here report a pathogenic variant of GATA4 in a 46,XY DSD patient with an atrial septal defect, identified by whole‐exome sequencing to be c.487C>T (p.Pro163Ser). This mutation resulted in reduced transcriptional activity of the downstream gene. When we compared this transcriptional activity level with other GATA4 variants, those that had been identified in patients with cardiac defects and DSD showed less activity than those in patients with cardiac defect only. This suggests that the normal development of the heart requires more strict regulation of GATA4 transcription than testicular development. Further, when the different variants were co‐expressed with wild‐type, the transcriptional activities were consistently lower than would be expected from an additive effect, suggesting a dominant‐negative impact of the variant via dimer formation of the GATA4 protein. Since these pathogenic GATA4 variants are occasionally identified in healthy parents, a threshold model of quantitative traits may explain the cardiac defect or DSD phenotypes that they cause. [ABSTRACT FROM AUTHOR]