Development of a novel prediction model for carriage of BRCA1/2 pathogenic variant in Japanese patients with breast cancer based on Japanese organization of hereditary breast and ovarian cancer registry data.

Purpose: With the increasing demand for BRCA genetic testing, most existing prediction models were developed using data from individuals of European descent. This study aimed to identify clinicopathological factors of hereditary breast and ovarian cancer (HBOC) syndrome and develop the first Japanese-specific prediction model for BRCA pathogenic variant carriers in Japan.

Methods: We utilized data from 3072 Japanese patients with breast cancer aggregated by the Japanese Organization of Hereditary Breast and Ovarian Cancer registry.

High-risk pathogenic germline variants in blood relatives of BRCA1/2 negative probands.

Background: Tailored, preventive cancer care requires the identification of pathogenic germline variants (PGVs) among potentially at-risk blood relatives (BRs). Cascade testing is carried out for BRs of probands who are positive for PGVs of an inherited cancer but not for negative probands. This study was conducted to examine the prevalence of PGVs for BRs of PGV-negative probands.

DiGeorge syndrome presenting with palmoplantar pustules: Comparative analysis of serum IL-22, NETs and IL-8 with usual palmoplantar pustulosis.

DiGeorge syndrome, also known as 22q11.2 deletion syndrome, shows cellular immunodeficiency due to by thymic hypoplasia and hypocalcemia caused by hypoparathyroidism. It was reported that erythrodermic psoriasis occurred in a patient with 22q11 deletion syndrome.

Factors associated with recurrence of bleb-related infections.

Purpose: To identify the risk factors for a recurrence of a bleb-related infection (BRI).

Study Design: Retrospective cohort study.

Methods: The medical records of all patients diagnosed with BRI at Gifu University Hospital between January 1989 and December 2020 were reviewed.

Two Cases of anti-PIT-1 Hypophysitis Exhibited as a Form of Paraneoplastic Syndrome not Associated With Thymoma.

Anti-pituitary-specific transcription factor 1 (PIT-1) hypophysitis (anti-PIT-1 antibody syndrome) is a thymoma-associated autoimmune disease characterized by acquired growth hormone (GH), prolactin (PRL), and thyrotropin (TSH) deficiencies due to autoimmunity against PIT-1. Ectopic expression of PIT-1 in the thymoma plays a causal role in development of the disease. Here, we report 2 cases of anti-PIT-1 hypophysitis exhibiting as a form of paraneoplastic syndrome with conditions other than thymoma.

BRCAness as a prognostic indicator in patients with early breast cancer.

BRCAness is defined as a phenotypic copy of germline BRCA mutations, which describes presence of homologous recombination defects in sporadic cancers. We detected BRCAness by multiplex ligation-dependent probe amplification (MLPA) and explored whether BRCAness can be used as a predictor of prognosis. BRCAness status was classified for total 121 breast cancer patients.

A Retrospective Analysis of the Relationship Between the Result of BRCA1/2 Genetic Testing and Surgical Method Selection in Japan.

Background: We studied the extent of BRCA1/2 genetic testing to help select the surgical approach for patients with breast cancer in Japan remains unclear.

Patients And Methods: The study subjects were female patients with primary unilateral invasive breast cancer considered as candidates for breast-conserving surgery who underwent preoperative BRCA1/2 genetic testing. A retrospective analysis was performed on the results of BRCA1/2 genetic testing and surgical method selection using national registration data from the Japanese Hereditary Breast and Ovarian Cancer Syndrome Consortium.

Prevalence of disease-causing genes in Japanese patients with -wildtype hereditary breast and ovarian cancer syndrome.

Panel sequencing of susceptibility genes for hereditary breast and ovarian cancer (HBOC) syndrome has uncovered numerous germline variants; however, their pathogenic relevance and ethnic diversity remain unclear. Here, we examined the prevalence of germline variants among 568 Japanese patients with -wildtype HBOC syndrome and a strong family history. Pathogenic or likely pathogenic variants were identified on 12 causal genes for 37 cases (6.

Thinning rates of retinal nerve layer and ganglion cell-inner plexiform layer in various stages of normal tension glaucoma.

Aims: To compare the changes in the macular retinal nerve fibre layer (mRNFL), macular ganglion cell layer and inner plexiform layer (mGCIPL), and circumpapillary retinal nerve fibre layer (cpRNFL) in various stages of normal tension glaucoma (NTG) using spectral domain optical coherence tomography.

Methods: Eyes with NTG (n=218) were assigned into three groups based on initial mean deviation (MD) as follows: mild (MD>-6 dB), moderate (-6 dB≥MD≥-12 dB) and severe (-12 dB>MD>-20 dB). Annual rates of change in mRNFL, mGCIPL and cpRNFL thickness were calculated by linear regression analysis.

[Hereditary Breast and Ovarian Cancer Syndrome].

Recently, olaparib(brand name: Lynparza Tablets)-a PARP inhibitor-has been approved for national health insurance coverage in Japan as a drug for unresectable or recurrent, BRCA1/2-positive, HER2-negative breast cancer in patients with a history of cancer chemotherapy. The addition of BRCA1/2 genetic testing as a companion diagnostic tool to the health insurance coverage is of considerable significance as a spearhead of health insurance medical care for all different types of hereditary tumors. However, several problems related to this companion diagnostic test have emerged, including the estab- lishment of a genetic counseling system and handling of BRCA1/2 genetic tests performed at the patients' own expense.

Analysis of clinical characteristics of breast cancer patients with the Japanese founder mutation L63X.

and are high-penetrance inherited genes; different founder mutations have been reported in various areas and races. By using trial registration data from the Japanese hereditary breast and ovarian cancer syndrome (HBOC) consortium, we aimed to explore the clinicopathological characteristics of breast cancer patients with the Japanese founder mutation L63X. We found 88 carriers, 76 carriers, and one carrier of both and .

The clinical impact of MRI screening for BRCA mutation carriers: the first report in Japan.

Background: There is no consensus on the appropriate surveillance for high-risk women with breast cancer in Japan. We investigated their imaging features and pathological characteristics to build a proper surveillance system for asymptomatic high-risk individuals in the future.

Methods: We retrospectively reviewed 93 female (median age 43 years) BRCA1 and BRCA2 mutation carriers from our institutional clinical database from 2011 to 2017.

BRCA1/BRCA2 mutations in Japanese women with ductal carcinoma in situ.

Background: Ductal carcinoma in situ (DCIS) is considered a component of the clinical spectrum of breast cancer even in those with BRCA1/2 mutation. The aim of this study was to report the feature of DCIS raised in Japanese women with BRCA1/2 mutations.

Methods: A total of 325 Japanese women with breast cancer (BC) (with or without invasive cancer) were referred for genetic counseling and underwent genetic testing for mutations in the BRCA1 and BRCA2 genes in Showa University Hospital between December 2011 and August 2016.

Correction: Genetic and clinical characteristics in Japanese hereditary breast and ovarian cancer: first report after establishment of HBOC registration system in Japan.

Correction to: Journal of Human Genetics advance online publication, 08 November 2017; https://doi.org/10.1038/s10038-017-0355-1.

Genetic and clinical characteristics in Japanese hereditary breast and ovarian cancer: first report after establishment of HBOC registration system in Japan.

The hereditary breast and ovarian cancer (HBOC) registration system of Japan was established by the Japanese HBOC Consortium. The first trial was registered in 2015 in four institutions to which some registration committee members belonged. We analyzed the information of 830 Japanese pedigrees, who underwent BRCA1/2 genetic testing, including mutation carriers with BRCA1 (N = 127) and BRCA2 (N = 115), and their families.

A survey on awareness of genetic counseling for non-invasive prenatal testing: the first year experience in Japan.

The purpose of this study is to summarize the results from a survey on awareness of genetic counseling for pregnant women who wish to receive non-invasive prenatal testing (NIPT) in Japan. As a component of a clinical study by the Japan NIPT Consortium, genetic counseling was conducted for women who wished to receive NIPT, and a questionnaire concerning both NIPT and genetic counseling was given twice: once after pre-test counseling and again when test results were reported. The responses of 7292 women were analyzed.

Intracerebroventricular administration of C-type natriuretic peptide suppresses food intake via activation of the melanocortin system in mice.

C-type natriuretic peptide (CNP) and its receptor are abundantly distributed in the brain, especially in the arcuate nucleus (ARC) of the hypothalamus associated with regulating energy homeostasis. To elucidate the possible involvement of CNP in energy regulation, we examined the effects of intracerebroventricular administration of CNP on food intake in mice. The intracerebroventricular administration of CNP-22 and CNP-53 significantly suppressed food intake on 4-h refeeding after 48-h fasting.

Differentiation of human embryonic stem cells and human induced pluripotent stem cells into steroid-producing cells.

Although there have been reports of the differentiation of mesenchymal stem cells and mouse embryonic stem (ES) cells into steroid-producing cells, the differentiation of human ES/induced pluripotent stem (iPS) cells into steroid-producing cells has not been reported. The purpose of our present study was to establish a method for inducing differentiation of human ES/iPS cells into steroid-producing cells. The first approach we tried was embryoid body formation and further culture on adherent plates.

A case of myelolipoma with bilateral adrenal hyperaldosteronism cured after unilateral adrenalectomy.

Myelolipomas are adrenal tumors composed of both adipose and hematopoietic tissues which are rarely associated with primary aldosteronism (PA). Here, we report a case of myelolipoma associated with PA. Aldosterone hypersecretion from bilateral adrenal glands had been confirmed by adrenal venous sampling and pathological analyses, but PA was clinically cured after surgical removal of the unilateral adrenal gland together with the myelolipoma that was not producing aldosterone.

Significance of adrenocorticotropin stimulation test in the diagnosis of an aldosterone-producing adenoma.

Context: Adrenal venous sampling is the "gold standard" test in the diagnosis of an aldosterone-producing adenoma (APA) among patients with primary aldosteronism (PA) but is available only in specialized medical centers. Meanwhile, an APA is reported to be generally more sensitive to ACTH than idiopathic hyperaldosteronism.

Objective: The aim was to evaluate the diagnostic accuracy of the ACTH stimulation test in the diagnosis of an APA among those with suspicion of PA.

C-type natriuretic peptide as a new regulator of food intake and energy expenditure.

The physiological implication of C-type natriuretic peptide (CNP) including energy metabolism has not been elucidated, because of markedly short stature in CNP-null mice. In the present study we analyzed food intake and energy expenditure of CNP-null mice with chondrocyte-targeted CNP expression (CNP-Tg/Nppc(-/-) mice), in which marked skeletal dysplasia was rescued, to investigate the significance of CNP under minimal influences of skeletal phenotypes. In CNP-Tg/Nppc(-/-) mice, body weight and body fat ratio were reduced by 24% and 32%, respectively, at 20 wk of age, and decreases of blood glucose levels during insulin tolerance tests were 2-fold exaggerated at 17 wk of age, as compared with CNP-Tg/Nppc(+/+) mice.