BACKGROUND Hereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome often associated with germline mutations in the CDH1 gene. However, the frequency of CDH1 mutations is low in patients with HDGC in East Asian countries. Herein, we report three cases of HDGC harboring a missense CDH1 variant, c.1679C>G, from a single Japanese family. CASE SUMMARY A 26-year-old female (Case 1) and a 51-year-old male (father of Case 1), who had a strong family history of gastric cancer, were diagnosed with advanced diffuse gastric cancer. After genetic counselling, a 25-year-old younger brother of Case 1 underwent surveillance esophagogastroduodenoscopy that detected small signet ring cell carcinoma foci as multiple pale lesions in the gastric mucosa. Genetic analysis revealed a CDH1 c.1679C>G variant in all three patients. CONCLUSION It is important for individuals suspected of having HDGC to be actively offered genetics evaluation. This report will contribute to an increased awareness of HDGC.

Background: Chromodomain helicase DNA-binding (CHD) proteins play important roles in developmental processes. CHD3, a member of the CHD family of proteins, was reported to be a cause of a neurodevelopmental syndrome by Snijders Blok et al., but only a small number of probands have been reported.Case report: The patient was a 9-year-old female with severe intellectual disability, speech impairment, autism, joint laxity and dysmorphisms. Whole exome sequencing revealed a de novo missense variant in CHD3 (NM_001005273:exon18: c.2896C > T:p. R966W). Conclusion:We report a case with a pathogenic variant in the CHD3 gene. Our report indicates that CHD3 analysis is helpful for diagnosis of the cases with neurodevelopmental disorders, joint laxity, and coarse facial phenotype.

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Vascular Ehlers–Danlos syndrome (vEDS) is a hereditary connective tissue disorder (HCTD) characterized by arterial dissection/aneurysm/rupture, sigmoid colon rupture, or uterine rupture. Diagnosis is confirmed by detecting heterozygous variants in COL3A1. This is the largest Asian case series and the first to apply an amplification‐based next‐generation sequencing through custom panels of causative genes for HCTDs, including a specific method of evaluating copy number variations. Among 429 patients with suspected HCTDs analyzed, 101 were suspected to have vEDS, and 33 of them (32.4%) were found to have COL3A1 variants. Two patients with a clinical diagnosis of Loeys–Dietz syndrome and/or familial thoracic aortic aneurysm and dissection were also found to have COL3A1 variants. Twenty cases (57.1%) had missense variants leading to glycine (Gly) substitutions in the triple helical domain, one (2.9%) had a missense variant leading to non‐Gly substitution in this domain, eight (22.9%) had splice site alterations, three (8.6%) had nonsense variants, two (5.7%) had in‐frame deletions, and one (2.9%) had a multi‐exon deletion, including two deceased patients analyzed with formalin‐fixed and paraffin‐embedded samples. This is a clinically useful system to detect a wide spectrum of variants from various types of samples.

Cutaneous polyarteritis nodosa (CPAN) is characterized by a necrotizing vasculitis of small and medium-sized arteries in the skin, which can be associated with fever, arthralgia, myalgia, and neuropathy, but, unlike polyarteritis nodosa (PAN), there is no visceral involvement. CPAN is rare in childhood. We report two siblings who developed CPAN during childhood. Interestingly, both had Mediterranean fever gene (MEFV) mutation, i.e. heterozygous E148Q. They also shared HLA-A24, -DR15 alleles. Simultaneous occurrence of MEFV mutation and HLA alleles with CPAN has never been reported in Japan. These cases could provide some hereditary clue for the development of CPAN.