Purpose: Radio-Tartaglia syndrome (RTS; Mendelian Inheritance in Man [MIM]: 619312) is a rare neurodevelopmental disorder with few reported cases and limited research. It has recently been reported that the clinical features of RTS overlap with those of 1p36 deletion syndrome (1p36DS), a common chromosomal deletion characterized by clinical and molecular heterogeneity. This study aims to report on a Korean patient with RTS and compare the clinical and molecular features with those of patients with 1p36DS. Methods: A 3-year-old boy was brought to the hospital and underwent whole genome sequencing to evaluate developmental delay and multiple anomalies. This led to the identification of a de novo truncating variant in SPEN. We retrospectively investigated cases of 1p36DS that were either newly diagnosed at our institution or previously reported in the literature and databases. Results: The clinical profile of RTS includes developmental delay/intellectual disability, hypotonia, feeding difficulties, congenital heart defects, and facial dysmorphisms. SPEN is frequently found within the deleted region associated with 1p36DS. However, in all reported Korean cases of 1p36DS, the deletions were distal and did not involve SPEN; despite this, the clinical features of the disorder overlap considerably with those of RTS. Conclusion SPEN is a newly identified gene that plays a role in various developmental processes. Therefore, it is essential to include SPEN in genetic testing when diagnosing patients suspected of having a neurodevelopmental disorder. Additional research is required to explore the molecular and clinical features, as well as the prognosis, of patients with either an isolated SPEN mutation or one that co-occurs with 1p36DS.

Purpose: To investigate the outcomes of brolucizumab reinjection after intraocular inflammation (IOI) development. Methods: This retrospective study analyzed patients with brolucizumab injections from April 2021 to January 2024. Patients who developed IOI after brolucizumab were included and categorized into subgroups depending on reinjection, discontinuation, and further IOI development. Results: A total of 472 eyes of 432 patients received brolucizumab injections. Thirty-eight cases developed IOI at least once, and 25 continued brolucizumab. Sixteen cases had no more IOI events, and nine experienced a second or more IOI events. Among the nine cases, three maintained brolucizumab injections despite IOI recurrence. The incidence of IOI was 8.1% based on the number of eyes (38 of 472 eyes) and 2.0% based on the number of brolucizumab injections (50 of 2,468 injections). The incidence of occlusive retinal vasculitis was 0.2% (1 of 472 eyes). The recurrence rate was 23.7% (9 of 38 eyes). The average number of injections between the first brolucizumab injection and the injection date on which IOI first developed was 2.15 times in the no-reinjection group, 3.44 times in the no-IOI-recurrence group, and 2.0 times in the second-IOI-episode group. Time to IOI occurrence in cases with first IOI episode was 18.60 ± 16.73 days, with 15 cases developing IOI within 1 week. Conclusions This study elucidates the real-world incidence of brolucizumab associated IOIs, with a description of information related to reinjections after the IOI episodes. A comprehensive understanding of brolucizumab reinjection is essential for its optimal utilization.

Purpose: To investigate the outcomes of brolucizumab reinjection after intraocular inflammation (IOI) development. Methods: This retrospective study analyzed patients with brolucizumab injections from April 2021 to January 2024. Patients who developed IOI after brolucizumab were included and categorized into subgroups depending on reinjection, discontinuation, and further IOI development. Results: A total of 472 eyes of 432 patients received brolucizumab injections. Thirty-eight cases developed IOI at least once, and 25 continued brolucizumab. Sixteen cases had no more IOI events, and nine experienced a second or more IOI events. Among the nine cases, three maintained brolucizumab injections despite IOI recurrence. The incidence of IOI was 8.1% based on the number of eyes (38 of 472 eyes) and 2.0% based on the number of brolucizumab injections (50 of 2,468 injections). The incidence of occlusive retinal vasculitis was 0.2% (1 of 472 eyes). The recurrence rate was 23.7% (9 of 38 eyes). The average number of injections between the first brolucizumab injection and the injection date on which IOI first developed was 2.15 times in the no-reinjection group, 3.44 times in the no-IOI-recurrence group, and 2.0 times in the second-IOI-episode group. Time to IOI occurrence in cases with first IOI episode was 18.60 ± 16.73 days, with 15 cases developing IOI within 1 week. Conclusions This study elucidates the real-world incidence of brolucizumab associated IOIs, with a description of information related to reinjections after the IOI episodes. A comprehensive understanding of brolucizumab reinjection is essential for its optimal utilization.

Background: An increased incidence of hair loss disorders has been noted among patients with coronavirus disease 2019 (COVID-19) and individuals vaccinated against COVID-19. However, research involving large populations on this topic is lacking. Objective: To investigate the risks associated with developing hair loss disorders in patients with COVID-19 and individuals vaccinated against COVID-19. Methods: This nationwide, population-based, cross-sectional study included patients diagnosed with COVID-19 and healthy individuals without a history of COVID-19 infection registered in the Korean National Health Insurance Service (NHIS) database between January 1, 2021, and December 31, 2021. COVID-19 infection and vaccine databases were integrated using this NHIS database. The odds ratios of hair loss disorders were compared using multivariate logistic regression models. Results: COVID-19 infection was associated with an increased risk of total alopecia (adjusted odds ratio [aOR], 1.076; 95% confidence interval [CI], 1.002–1.156), although this association was not significant after propensity score matching. No significant associations were found between COVID-19 infection and alopecia areata or telogen effluvium. However, COVID-19 vaccination was positively correlated with total alopecia (aOR, 1.266; 95% CI, 1.191–1.346), alopecia areata (aOR, 1.243; 95% CI, 1.154–1.339), and telogen effluvium (aOR, 1.495; 95% CI, 1.133–1.974). Conclusion COVID-19 vaccination was positively correlated with hair loss disorders but not COVID-19 infection. However, given the advantages of vaccines in reducing COVID-19 mortality and morbidity, alopecia may be relatively reversible and less severe. Physicians need to understand the benefits and possible side effects of the COVID-19 vaccine.

Background: MUTYH-associated polyposis is an autosomal recessive disorder associated with an increased lifetime risk of colorectal cancer and a moderately increased risk of ovarian, bladder, breast, and endometrial cancers. We analyzed the carrier frequency and estimated the incidence of MUTYH-associated polyposis in East Asian and Korean populations, for which limited data were previously available. Methods: We examined 125,748 exomes from the gnomAD database, including 9,197 East Asians, and additional data from 5,305 individuals in the Korean Variant Archive and 1,722 in the Korean Reference Genome Database. All MUTYH variants were interpreted according to the American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines and the Sequence Variant Interpretation guidelines from ClinGen. Results: The global carrier frequency of MUTYH-associated polyposis was 1.29%, with Europeans (non-Finnish) having the highest frequency of 1.86% and Ashkenazi Jews the lowest at 0.06%. East Asians and Koreans had a carrier frequency of 0.35% and 0.37% and an estimated incidence of 1 in 330,409 and 1 in 293,304 in Koreans, respectively, which were substantially lower than the global average of 1 in 24,160 and the European (nonFinnish) incidence of 1 in 11,520. Conclusions This was the first study to investigate the frequency of carriers of MUTYH-associated polyposis in East Asians, including specific subgroups, utilizing gnomAD and a Korean genome database. Our data provide valuable reference information for future investigations of MUTYH-associated polyposis to understand the genetic diversity and specific variants associated with this condition in East Asian populations.

Background: Citrin deficiency is an autosomal recessive disorder caused by pathogenic variants in SLC25A13, presenting with various age-dependent clinical phenotypes and a broad spectrum of severity. However, few studies have examined the frequency and prevalence of citrin deficiency. We aimed to analyze the carrier frequency and disease prevalence in East Asian populations and Koreans. Methods: We comprehensively reviewed the literature and conducted a cross-sectional study to analyze genomic databases, including the Genome Aggregation Database (gnomAD), Korean Variant Archive (KOVA), and Tohoku Medical Megabank Organization (ToMMo), to identify pathogenic SLC25A13 variants in East Asian populations. A founder 3-kilobase (kb) insertion in intron 16 of SLC25A13 was investigated using whole-genome sequencing data from 681 Koreans with the Linux grep command. Results: Twenty-three pathogenic SLC25A13 variants were identified, with c.852_855del being the most common. Analysis of data from 17,501 East Asian individuals in the gnomAD and ToMMo databases revealed a carrier frequency of 1 in 62 people. Analysis of data from 7,214 individuals in the gnomAD and KOVA databases revealed a carrier frequency of 1 in 86, corresponding to an estimated disease prevalence of 1 in 29,502.c.1177+1G > A was identified as the most prevalent pathogenic variant in Koreans. The 3 kb insertion in intron 16 was detected in three out of 681 individuals, indicating a carrier frequency of 1 in 228. Conclusions The high carrier frequency of citrin deficiency in East Asians highlights the need for enhanced genetic screening and counseling, particularly in Korea, providing a valuable reference for future studies on genetic diversity and pathogenic variants in this population.

Purpose: Radio-Tartaglia syndrome (RTS; Mendelian Inheritance in Man [MIM]: 619312) is a rare neurodevelopmental disorder with few reported cases and limited research. It has recently been reported that the clinical features of RTS overlap with those of 1p36 deletion syndrome (1p36DS), a common chromosomal deletion characterized by clinical and molecular heterogeneity. This study aims to report on a Korean patient with RTS and compare the clinical and molecular features with those of patients with 1p36DS. Methods: A 3-year-old boy was brought to the hospital and underwent whole genome sequencing to evaluate developmental delay and multiple anomalies. This led to the identification of a de novo truncating variant in SPEN. We retrospectively investigated cases of 1p36DS that were either newly diagnosed at our institution or previously reported in the literature and databases. Results: The clinical profile of RTS includes developmental delay/intellectual disability, hypotonia, feeding difficulties, congenital heart defects, and facial dysmorphisms. SPEN is frequently found within the deleted region associated with 1p36DS. However, in all reported Korean cases of 1p36DS, the deletions were distal and did not involve SPEN; despite this, the clinical features of the disorder overlap considerably with those of RTS. Conclusion SPEN is a newly identified gene that plays a role in various developmental processes. Therefore, it is essential to include SPEN in genetic testing when diagnosing patients suspected of having a neurodevelopmental disorder. Additional research is required to explore the molecular and clinical features, as well as the prognosis, of patients with either an isolated SPEN mutation or one that co-occurs with 1p36DS.

Purpose: Radio-Tartaglia syndrome (RTS; Mendelian Inheritance in Man [MIM]: 619312) is a rare neurodevelopmental disorder with few reported cases and limited research. It has recently been reported that the clinical features of RTS overlap with those of 1p36 deletion syndrome (1p36DS), a common chromosomal deletion characterized by clinical and molecular heterogeneity. This study aims to report on a Korean patient with RTS and compare the clinical and molecular features with those of patients with 1p36DS. Methods: A 3-year-old boy was brought to the hospital and underwent whole genome sequencing to evaluate developmental delay and multiple anomalies. This led to the identification of a de novo truncating variant in SPEN. We retrospectively investigated cases of 1p36DS that were either newly diagnosed at our institution or previously reported in the literature and databases. Results: The clinical profile of RTS includes developmental delay/intellectual disability, hypotonia, feeding difficulties, congenital heart defects, and facial dysmorphisms. SPEN is frequently found within the deleted region associated with 1p36DS. However, in all reported Korean cases of 1p36DS, the deletions were distal and did not involve SPEN; despite this, the clinical features of the disorder overlap considerably with those of RTS. Conclusion SPEN is a newly identified gene that plays a role in various developmental processes. Therefore, it is essential to include SPEN in genetic testing when diagnosing patients suspected of having a neurodevelopmental disorder. Additional research is required to explore the molecular and clinical features, as well as the prognosis, of patients with either an isolated SPEN mutation or one that co-occurs with 1p36DS.