Establishment of in-hospital clinical network for patients with neurofibromatosis type 1 in Nagoya University Hospital.

Neurofibromatosis type 1 (NF1) is a genetic multisystem disorder. Clinicians must be aware of the diverse clinical features of this disorder in order to provide optimal care for it. We have set up an NF1 in-hospital medical care network of specialists regardless of patient age, launching a multidisciplinary approach to the disease for the first time in Japan. From January 2014 to December 2020, 246 patients were enrolled in the NF1 patient list and medical records. Mean age was 26.0 years ranging from 3 months to 80 years. The number of patients was higher as age at first visit was lower. There were 107 males (41%) and 139 females. After 2011, the number of patients has increased since the year when the medical care network was started. Regarding orthopedic signs, scoliosis was present in 60 cases (26%), and bone abnormalities in the upper arm, forearm, and tibia in 8 cases (3.5%). Neurofibromas other than cutaneous neurofibromas were present in 90 cases (39%), and MPNST in 17 cases (7.4%). We launched a multidisciplinary NF1 clinic system for the first time in Japan. For patients with NF1, which is a hereditary and systemic disease associated with a high incidence of malignant tumors, it will be of great benefit when the number of such clinics in Japan and the rest of Asia is increased.

Generation and analysis of novel Reln-deleted mouse model corresponding to exonic Reln deletion in schizophrenia.

AIM: A Japanese individual with schizophrenia harboring a novel exonic deletion in RELN was recently identified by genome-wide copy-number variation analysis. Thus, the present study aimed to generate and analyze a model mouse to clarify whether Reln deficiency is associated with the pathogenesis of schizophrenia. METHODS: A mouse line with a novel RELN exonic deletion (Reln-del) was established using the CRISPR/Cas9 method to elucidate the underlying molecular mechanism. Subsequently, general behavioral tests and histopathological examinations of the model mice were conducted and phenotypic analysis of the cerebellar granule cell migration was performed. RESULTS: The phenotype of homozygous Reln-del mice was similar to that of reeler mice with cerebellar atrophy, dysplasia of the cerebral layers, and abrogated protein levels of cerebral reelin. The expression of reelin in heterozygous Reln-del mice was approximately half of that in wild-type mice. Conversely, behavioral analyses in heterozygous Reln-del mice without cerebellar atrophy or dysplasia showed abnormal social novelty in the three-chamber social interaction test. In vitro reaggregation formation and neuronal migration were severely altered in the cerebellar cultures of homozygous Reln-del mice. CONCLUSION: The present results in novel Reln-del mice modeled after our patient with a novel exonic deletion in RELN are expected to contribute to the development of reelin-based therapies for schizophrenia.

Clinical Features and Long-Term Outcomes of Living Donors of Liver Transplantation Who Developed Psychiatric Disorders.

BACKGROUND In the field of living donor liver transplantation (LDLT), it is important to ensure donor's psychological well-being. We report on clinical features and long-term outcomes of LDLT donors who developed psychiatric disorders after their donor operations. Additionally, we compare patient backgrounds, as well as surgical and perioperative aspects between LDLT donors with and without postoperative psychiatric complications. MATERIAL AND METHODS Between November 1998 and March 2018, we identified 254 LDLT donors at our hospital. Among these, we investigated those who had newly developed psychiatric complications and required psychiatric treatment after donor operation. RESULTS The median duration of follow-up was 4 years. Sixty-five donors were lost to follow-up. Eight donors (3.1%) developed postoperative psychiatric complications, including major depressive disorder in 4, panic disorder in 2, conversion disorder and panic disorder in 1, and adjustment disorder in 1. The median duration from donor surgery to psychiatric diagnosis was 104.5 days (range, 12 to 657 days) and the median treatment duration was 18 months (range, 3 to 168 months). Of those, 3 donors required psychiatric treatment over 10 years, and 4 donors remained under treatment. The duration of hospital stay after donor operation was significantly longer and perioperative complications with Clavien classification greater than grade IIIa were more frequent in donors with psychiatric complications than in those without psychiatric complications (P=0.02 and P=0.006, respectively). CONCLUSIONS Accurate diagnosis and appropriate treatment for psychiatric disorders by psychiatrists and psychologists are important during LDLT donor follow-up. Minimization of physiological complications might be important to prevent postoperative psychiatric complications in LDLT donors.