Aim:To search for patched homologue 1 (PTCH1) mutations in four families with basal cell nevus syndrome (BCNS).Methods:Mutation analysis ofPTCH1in unrelated Japanese families affected with BCNS was carried out by direct sequencing.Results:Six novelPTCH1mutations, 833G→A in exon 6, 1415C→A and 1451G→T in exon 10, 2798delC in exon 17, 2918–2925dupAGTTCCCT in exon 18 and 3956C→A in exon 23, were identified.Conclusions:Among the sixPTCH1mutations, two frameshift mutations (2798delC and 2918–2925dupAGTTCCCT) and one nonsense mutation (833G→A) are predicted to lead to premature termination ofPTCH1protein translation. Three simultaneous mutations, 1415C→A (A472D) and 1451G→T (G484V) in exon 10, and 3956G→A (R1319H) in exon 23, were found on one allele in only affected members in one family and none of them were found among 90 unrelated healthy Japanese. The three mutations on one chromosome may have resulted from errors in the recombinational repair process and this is the first report on thePTCH1mutations due to such a mechanism.

Although videofluorography (VFG) is an effective tool for evaluating swallowing functions, its accurate evaluation requires considerable time and effort. This study aimed to create a deep learning model for automated bolus segmentation on VFG images of patients with healthy swallowing and dysphagia using the artificial intelligence deep learning segmentation method, and to assess the performance of the method. VFG images of 72 swallowing of 12 patients were continuously converted into 15 static images per second. In total, 3910 images were arbitrarily assigned to the training, validation, test 1, and test 2 datasets. In the training and validation datasets, images of colored bolus areas were prepared, along with original images. Using a U-Net neural network, a trained model was created after 500 epochs of training. The test datasets were applied to the trained model, and the performances of automatic segmentation (Jaccard index, Sørensen–Dice coefficient, and sensitivity) were calculated. All performance values for the segmentation of the test 1 and 2 datasets were high, exceeding 0.9. Using an artificial intelligence deep learning segmentation method, we automatically segmented the bolus areas on VFG images; our method exhibited high performance. This model also allowed assessment of aspiration and laryngeal invasion.

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Congenital tooth agenesis is a common anomaly in human development. We performed exome sequence analysis of genomic DNA collected from Japanese patients with tooth agenesis and their relatives. We found a novel single-nucleotide insertion in the LRP6 gene, the product of which is involved in Wnt/β-catenin signaling as a coreceptor for Wnt ligands. The single-nucleotide insertion results in a premature stop codon in the extracellular region of the encoded protein.

Congenital tooth agenesis is a common anomaly in humans. We investigated the etiology of human tooth agenesis by exome analysis in Japanese patients, and found a previously undescribed heterozygous deletion (NM_002448.3(MSX1_v001):c.433_449del) in the first exon of the MSX1 gene. The deletion leads to a frameshift and generates a premature termination codon. The truncated form of MSX1, namely, p.(Trp145Leufs*24) lacks the homeodomain, which is crucial for transcription factor function.