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Coastal boulders are often formed by tsunamis and storm surges and thus provide valuable insights into the dynamics of past inundation events. However, the mapping of these boulders has been constrained by inherent limitations in the speed and precision of manual processes. In this study, we introduced a novel approach for boulder mapping by integrating an unmanned aerial vehicle with a mask region-based convolutional neural network that enables the rapid and precise detection and volume calculation of boulders distributed along coastlines. The approach was validated on Ishigaki Island, Okinawa, Japan, and showed high precision in the detection and measurement of boulders, achieving a high F1-score of 0.863 for the target boulders. The digital surface model yielded more realistic and precise volume calculations than the traditional approximation approach, providing more accurate information for understanding the transport processes of coastal boulders during inundation events. This approach enhances our understanding of past inundation events and provides a practical tool for ongoing coastal monitoring and disaster response. Furthermore, it serves as a baseline model for future research in automated boulder mapping.

Information on palaeo-tsunami magnitude is scientifically and socially essential to mitigate tsunami risk. However, estimating palaeo-tsunami parameters (e.g., inundation distance) from sediments is not simple because tsunami deposits reflect complex transport processes. Here, we show a new approach to estimate tsunami inundation distance based on the mixture ratio of gravels from several sources in tsunami deposits. We measured the roundness of source gravels in modern beach and fluvial deposits in a coastal valley in Japan through image analysis and then calculated the mixture ratio of both sediment types in tsunami deposits. Normalising the mixture ratios by inundation distances revealed an abrupt change in the mixture ratio at a constant percentile, regardless of tsunami magnitude. This relation allowed estimation of the inundation distance of palaeo-tsunamis during the last 4000 years.

Heterozygous variants in TUBB encoding one of β-tubulin isotypes are known to cause two overlapping developmental brain disorders, complex cortical dysplasia with other brain malformations (CDCBM) and congenital symmetric circumferential skin creases (CSCSC). To date, six cases of CSCSC and eight cases of CDCBM caused by nine heterozygous variants have been reported. Here we report two cases with novel de novo missense TUBB variants (NM_178014.4:c.863A>G, p.(Glu288Gly) and c.869C>T, p.(Thr290Ile)). Case 1 presented brain malformations consistent with tubulinopathies including abnormalities in cortex, basal ganglia, corpus callosum, brain stem, and cerebellum along with other systemic features such as coloboma, facial dysmorphisms, vesicoureteral reflux, hypoplastic kidney, and cutis laxa-like mild skin loosening. Another case presented abnormalities of the corpus callosum, brain stem, and cerebellum along with facial dysmorphisms. We reviewed previous literature and suggest the diversity of clinical findings of TUBB-related disorders.

Here we present four unrelated families with six individuals that have infantile-onset developmental delay/regression and epilepsy. Whole-exome sequencing revealed compound heterozygous mutations, c.[283G>A];[607G>A] in a gene encoding prolyl-tRNA synthetase (PARS2) in one family. Two pairs of compound heterozygous mutations, c.[151C>T];[1184T>G] and c.[707T>G];[594+1G>A], and a homozygous mutation, c.[500A>G];[500A>G], in a gene encoding asparaginyl-tRNA synthetase (NARS2) were also identified in the other three families. Mutations in genes encoding aminoacyl-tRNA synthetases cause gene-specific mitochondrial disorders. Biallelic PARS2 or NARS2 mutations are reported to cause Alpers' syndrome, which is an autosomal recessive neurodegenerative disorder characterized by psychomotor regression and epilepsy with variable degree of liver involvement. Moreover, it is known that NARS2 mutations cause various clinical phenotypes, including non-syndromic hearing loss, Leigh syndrome, intellectual disability with epilepsy and severe myopathy. The individuals with PARS2 and NARS2 mutations, we have reported here demonstrate similar neurological features as those previously reported, with diversity in clinical presentation such as hearing loss and seizure type. Our data broaden the clinical and mutational spectrum of PARS2- and NARS2-related disorders.

Variant annotations are crucial for efficient identification of pathogenic variants. In this study, we retrospectively analyzed the utility of four annotation tools (allele frequency, ClinVar, SpliceAI, and Phenomatcher) in identifying 271 pathogenic single nucleotide and small insertion/deletion variants (SNVs/small indels). Although variant filtering based on allele frequency is essential for narrowing down on candidate variants, we found that 13 de novo pathogenic variants in autosomal dominant or X-linked dominant genes are registered in gnomADv4.0 or 54KJPN, with an allele frequency of less than 0.001%, suggesting that very rare variants in large cohort data can be pathogenic de novo variants. Notably, 38.4% candidate SNVs/small indels are registered in the ClinVar database as pathogenic or likely pathogenic, which highlights the significance of this database. SpliceAI can detect candidate variants affecting RNA splicing, leading to the identification of four variants located 11 to 50 bp away from the exon–intron boundary. Prioritization of candidate genes by proband phenotype using the PhenoMatcher module revealed that approximately 95% of the candidate genes had a maximum PhenoMatch score ≥ 0.6, suggesting the utility of phenotype-based variant prioritization. Our results suggest that a combination of multiple annotation tools and appropriate evaluation can improve the diagnosis of rare diseases.

Geomagnetic excursions represent the dynamic nature of the geodynamo. Accumulated palaeomagnetic records indicate that such excursions are dominated by dipolar-fields, but exhibit different structures. Here we report a palaeomagnetic record from the varved sediments of Lake Suigetsu, central Japan, which reveals fine structures in the Laschamp Excursion and a new post-Laschamp excursion that coincides with the Δ 14 C maxima. The record’s high-resolution chronology provides IntCal20 mid-ages and varve-counted durations. Both excursions comprise multiple subcentennial directional-swings. Simulations of filtering effects on sediment-magnetisations demonstrate that this high-resolution record replicates most of the features in existing, lower-resolution Laschamp excursion records, including the apparent clockwise open-loop of the virtual geomagnetic pole pass. The virtual geomagnetic poles during the ‘swing’ phases make four clusters centred in hemispherically-symmetric regions, three of which encompass the virtual geomagnetic poles associated with the Laschamp Excursion recorded in lavas at various locations. The stationary dipolar-field sources under each cluster should have intermittently dominated one after another during the excursions.

Objectives Long‐term adrenocorticotropic therapy (LT‐ACTH), which consisted of 2‐4 weeks of daily injections of adrenocorticotropic hormone (ACTH) and subsequent months of weekly injections, was tried for relapsed West syndrome (WS) or other intractable epilepsies in small case reports. Our aim was to explore the efficacy of LT‐ACTH for preventing WS relapse, as well as the prevalence of its adverse events. Methods This is a retrospective, nationwide, multicenter case series of patients with WS who underwent LT‐ACTH. Clinical information of the patients and protocol of LT‐ACTH were collected from participating institutes in this study. We defined clinical response to ACTH as achievement of hypsarrhythmia and epileptic spasms resolution. Patients who responded to daily ACTH injections were identified and assessed whether they experienced WS relapse during/after the weekly ACTH injection period. The outcome was measured by the nonrelapse rate at 24 months after daily ACTH injections using the Kaplan‐Meier method. Results Clinical information of 16 children with WS was analyzed. The median age at LT‐ACTH initiation was 14.5 months (range: 7‐68 months). Thirteen (81%) patients had previously undergone conventional ACTH treatment. The LT‐ACTH regimens comprised a median of 16 days of daily injections (range: 11‐28 days) and 10 months of weekly injections (range: 3‐22 months). Seven patients experienced WS relapse during/after subsequent weekly ACTH period, and the nonrelapse rate at 24 months after daily injections was estimated at 60.6% (95% confidence interval: 32.3%‐80.0%). Height stagnation, hypertension, and irritability were observed; lethal adverse events were not reported. Significance Our study firstly explored the efficacy of LT‐ACTH for preventing WS relapse. LT‐ACTH might be a treatment option for patients with relapsed or intractable WS; however, we note that our study is limited by its small sample size and the lack of an appropriate control group.

Background The tricarboxylic acid (TCA) cycle is a sequence of catabolic reactions within the mitochondrial matrix, and is a central pathway for cellular energy metabolism. Genetic defects affecting the TCA cycle are known to cause severe multisystem disorders. Methods We performed whole exome sequencing of genomic DNA of a patient with progressive cerebellar and cerebral atrophy, hypotonia, ataxia, seizure disorder, developmental delay, ophthalmological abnormalities and hearing loss. We also performed biochemical studies using patient fibroblasts. Results We identified new compound heterozygous mutations (c.1534G > A, p.Asp512Asn and c.1997G > C, p.Gly666Ala) in ACO2, which encodes aconitase 2, a component of the TCA cycle. In patient fibroblasts, the aconitase activity was reduced to 15% of that of the control, and the aconitase 2 level decreased to 36% of that of the control. As such a decrease in aconitase 2 in patient fibroblasts was partially restored by proteasome inhibition, mutant aconitase 2 was suggested to be relatively unstable and rapidly degraded after being synthesized. In addition, the activity of the father‐derived variant of aconitase 2 (p.Gly666Ala), which had a mutation near the active center, was 55% of that of wild‐type. Conclusion The marked reduction of aconitase activity in patient fibroblasts was due to the combination of decreased aconitase 2 amount and activity due to mutations. Reduced aconitase activity directly suppresses the TCA cycle, resulting in mitochondrial dysfunction, which may lead to symptoms similar to those observed in mitochondrial diseases. The tricarboxylic acid (TCA) cycle is a sequence of catabolic reactions within the mitochondrial matrix, and is a central pathway for cellular energy metabolism. Genetic defects affecting the TCA cycle are known to cause severe multisystem disorders. We report new compound heterozygous mutations (c.1534G > A, p.D512N and c.1997G > C, p.G666A) in ACO2, which encodes aconitase 2, a component of the TCA cycle, in a patient with progressive cerebellar and cerebral atrophy, hypotonia, ataxia, seizure disorder, developmental delay, ophthalmological abnormalities and hearing loss.

Correction to: Journal of Human Genetics; doi:10.1038/jhg.2016.163; Published online 12 January 2017 In the version of this article initially published online, Supplementary Figure S2 incorrectly appears as Supplementary Figure S1. This error has now been rectified and the correct Supplementary Figure S1 appears in this erratum.

Whole exome sequencing/whole genome sequencing has accelerated the identification of novel genes associated with intellectual disabilities (ID), and RAB11A which encodes an endosomal small GTPase is among them. However, consequent neural abnormalities have not been studied, and pathophysiological mechanisms underlying the ID and other clinical features in patients harboring RAB11A variants remain to be clarified. In this study, we report a novel de novo missense variant in RAB11A, NM_004663.5: c . 98 G > C , which would result in NP_004654.1: p.(R33P) substitution, in a Japanese boy with severe ID and hypomyelination. Biochemical analyses indicated that the RAB11A-R33P is a gain-of-function, constitutively active variant. Accordingly, the introduction of the RAB11A-R33P promoted neurite extension in neurons like a known constitutively active variant Rab11A-Q70L. In addition, the RAB11A-R33P induced excessive branching with thinner processes in oligodendrocytes. These results indicate that the gain-of-function RAB11A-R33P variant in association with ID and hypomyelination affects neural cells and can be deleterious to them, especially to oligodendrocytes, and strongly suggest the pathogenic role of the RAB11A-R33P variant in neurodevelopmental impairments, especially in the hypomyelination.