OBJECTIVETo identify the ankyrin-B gene mutations that cause long QT syndrome (LQTS) and determine the prevalence of such mutations in Japanese patients with LQTS.

METHODSWe conducted a search for ankyrin-B gene mutation in 78 unrelated patients with LQTS (28 males and 50 females, aged 2 to 89 years). With informed consent from all the subjects and/or their parents, genomic DNA was purified from the white blood cells of the patients and amplified using polymerase chain reaction (PCR). Single-strand conformational polymorphism (SSCP) analysis of the amplified DNA was performed to screen for mutations and aberrant SSCP products were isolated and sequenced by dye terminator cycle sequencing method using an automated fluorescent sequencer. PCR and restriction fragment length polymorphism (PCR-RFLP) analysis was carried out to further confirm the missense mutations by comparison with samples from 150 normal healthy individuals.

RESULTSWe identified a T to A transition mutation at position 4,603 in exon 40, resulting in the substitution of arginine for a tryptophan at amino acid residue 1,535 (W1535R) in the regulatory domain of 220-kD ankyrin-B, which is a highly conserved domain shared by different species.

CONCLUSIONThis novel missense mutation in the ankyrin-B gene may be a cause of type 4 LQTS. Ankyrin-B gene mutation might not play the major role in LQTS in Japanese.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Amino Acid Substitution ; Ankyrins ; genetics ; Base Sequence ; Child ; Child, Preschool ; Exons ; Female ; Humans ; Long QT Syndrome ; genetics ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation, Missense ; Point Mutation

Background/Aims: Immune checkpoint blockade has recently been reported to be effective in treating microsatellite instability (MSI)-high tumors. Therefore, sufficient sampling of histological specimens is necessary in cases of unresectable pancreatic cancer (UR-PC). This multicenter study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for MSI evaluation in patients with UR-PC. Methods: A total of 89 patients with UR-PC who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or EUS-FNB using 22-G needles at three hospitals in Japan (2018–2021) were enrolled. Fifty-six of these patients (FNB 23 and FNA 33) were followed up or evaluated for MSI. Patient characteristics, UR-PC data, and procedural outcomes were compared between patients who underwent EUS-FNB and those who underwent EUS-FNA. Results: No significant difference in terms of sufficient tissue acquisition for histology was observed between patients who underwent EUS-FNB and those who underwent EUS-FNA. MSI evaluation was possible significantly more with tissue samples obtained using EUS-FNB than with tissue samples obtained using EUS-FNA (82.6% [19/23] vs. 45.5% [15/33], respectively; p<0.01). In the multivariate analysis, EUS-FNB was the only significant factor influencing the possibility of MSI evaluation. Conclusions EUS-FNB using a Franseen needle is desirable for ensuring sufficient tissue acquisition for MSI evaluation.