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Background/aim We have recently shown that oral recombinant methionase (o-rMETase) prevents obesity and diabetes onset in mice on a high-fat (HF) diet. The present study aimed to determine if o-rMETase can inhibit the onset of nonalcoholic fatty liver disease (NAFLD) onset in mice on a high-fat diet. Materials and methods Male C57BL/6J mice in the control group were fed a normal-fat diet (NFD) (+6.5% fat), and other mice were fed a high-fat (HF) diet (+34.3% fat). Then, the mice on the HF diet were divided into two dietary groups: i) HF+phosphate buffered saline (PBS) group, and ii) HF+o-rMETase group. Result The fatty change score in the livers of mice treated with HF+PBS increased to an average of 2.6 during the experimental period of 8 weeks. In contrast, the fatty change in the livers of mice on the HF+o-rMETase group had an average score of 0.92 (p=0.04, HF+PBS vs HF+o-rMETase). Conclusion o-rMETase inhibited the onset of NAFLD as well as prevented obesity and the onset of diabetes on a high-fat diet, offering a possibility of a new paradigm to prevent liver cirrhosis or liver cancer via NAFLD.

Aim: The purpose of this study was to see how important it was for the expression of liver fatty acid-binding protein (L-FABP) to be downregulated in hepatocellular carcinoma (HCC). Methods: Immunohistochemical labelling for L-FABP was performed on tissue microarrays from 146 instances of HCC. For each L-FABP-negative HCC, further immunohistochemical staining was performed using a representative whole-tissue section to confirm the downregulation of L-FABP expression and to assess the intratumoral heterogeneity of the staining pattern. Histological slides were examined and clinical data was gathered from the clinical files. On the tissue microarrays, immunohistochemical staining for cytokeratin (CK) 7, CK 19, \(\beta\)-catenin-catenin, glutamine synthetase (GS), and serum amyloid A (SAA) were also done. L-FABP-negative and L-FABP-positive HCC patients were compared in terms of clinicopathological characteristics. Furthermore, L-FABP and GS gene expression in HCC and cholangiocarcinoma (CC) cell lines were analyzed using real-time reverse transcription polymerase chain reaction. Mutation analysis of HNF1A (encoding hepatocyte nuclear factor 1 (HNF1)\(\alpha\)) was performed for L-FABP-negative HCC cases. Results: Sixteen (10.9%) of the 146 HCC patients tested negative for L-FABP. When we examined the correlation between the downregulation pattern of L-FABP and tumor size, most cases of smaller HCC (\(\le\)2 cm in diameter) exhibited focal downregulation, while most cases of larger HCC (> 2 cm in diameter) exhibited diffuse downregulation. The correlation was statistically significant (P = 0.036). When the HCC was smaller, the L-FABP-negative area often corresponded to a “nodule-in-nodule” appearance. Among the small HCC cases, tumor differentiation was significantly lower, and the frequency of intratumoral inflammation was significantly lower in L-FABP-negative cases than in L-FABP-positive cases (P = 0.032 and P = 0.009, respectively). The frequency of positivity for b-catenin and GS staining was significantly higher in L-FABP-negative cases of small HCC than in L-FABP-positive cases of small HCC (P = 0.009 and P = 0.000, respectively). Among six HCC cell lines examined, four showed higher expression of L-FABP, and the remaining two cell lines showed lower or no expression of L-FABP. Two of the 16 L-FABP-negative HCC cases possessed a mutation in exon 4 of HNF1A. Conclusion: In smaller HCC, L-FABP downregulation probably occurs because of phenotypic changes during tumor progression. Moreover, this downregulation correlated with tumor differentiation and intratumoral inflammation.

Nonalcoholic fatty liver disease (NAFLD) is a condition in which excessive fat builds up in the liver of a person who has never drank excessive alcohol. This disease includes simple steatosis and nonalcoholic steatohepatitis (NASH). The hepatic manifestation of the metabolic syndrome is known as NAFLD/NASH. Pediatric NAFLD has risen in recent years, along with an increase in the frequency of childhood obesity. The frequency of pediatric NAFLD is believed to be between 2.6 and 9.6 percent, and it is linked to sex, age, and ethnicity. The "two-hit" concept is largely recognised when it comes to the aetiology of NAFLD, and oxidative stress is assumed to play a key role in the second hit. Despite the importance of clinical symptoms, laboratory data, and imaging results, liver biopsy remains the gold standard for diagnosing NAFLD/NASH. In addition, liver biopsy is essential for assessing the degree of necro-inflammatory change and fibrosis in NASH. There are two forms of steatohepatitis (type 1 and type 2 NASH), with type 2 NASH being present in up to 51% of juvenile NAFLD patients. We and others have seen, however, that type 1 and 2 patterns frequently overlap. Despite the fact that medication has been investigated in clinical trials, diet and exercise remain the foundation of NAFLD/NASH treatment.

The gastrointestinal tract adenomyoma is an uncommon benign tumor-like disease. The second most common site is the small intestine, which commonly occurs in the periampullary region, although the lesion can also occur in the jejunum and ileum. While Vaterian adenomyoma is most commonly identified in adults, juvenile patients account for more than half of all documented instances of jejunal and ileal adenomyoma. The periampullary adenomyoma generally causes biliary obstruction or abdominal pain, whereas the jejunal and ileal adenomyoma generally causes intussusception or is discovered accidentally during surgery or autopsy. Histopathological study is critical in adenomyoma diagnosis since endoscopic and radiographic examinations show non-specific results. Adenomyoma is a pathological condition in which glandular structures of varying sizes are surrounded by interlacing smooth muscle bundles. The pathogenesis of adenomyoma is thought to be either a kind of hamartoma or a pancreatic heterotopia. Despite the fact that restricted resection is the most appropriate therapy, pancreaticoduodenectomy is frequently performed when the lesion arises in the periampullary region due to a preoperative misdiagnosis as a carcinoma. As a result, it's critical that physicians and pathologists keep up to date on the condition to prevent making incorrect diagnoses that lead to unneeded surgery.

Protein induced by vitamin K absence or antagonist II (PIVKA-II) is a possible hepatocellular carcinoma (HCC) specific marker, however it may also be generated by a limited number of stomach malignancies. PIVKA-II-producing stomach cancer has been recorded in 16 instances so far, two of which were reported by us and all of which were found in Japan. In virtually all instances, serum alpha-fetoprotein (AFP) levels are also elevated. In roughly 80% of instances, liver metastasis is found, and portal vein tumor thrombus is detected in roughly 20% of cases. It's often difficult to tell the difference between a metastatic liver tumor and HCC. Almost all cases appear to be advanced stomach cancer macroscopically. In many cases, a hepatoid pattern is present, as well as a moderately to poorly differentiated adenocarcinoma component. Immunohistochemical staining is frequently used to confirm the generation of PIVKA-II and AFP. The presence of liver metastasis influences treatment and prognosis, and individuals with liver metastasis have a poor prognosis. PIVKA-II may be generated by tumor cells during hepatocellular metaplasia.

Mucin-type O-glycosylation of serine or threonine residue in proteins is known to be one of the major post-translational modifications. In this study, two novel alkyl glycosides, N

Metastasis stands as the major obstacle for the survival from cancers. Nonetheless most existing anti-cancer drugs inhibit only cell proliferation, and discovery of agents having both anti-proliferative and anti-metastatic properties would be more beneficial. We previously reported the discovery of small-molecule Ras inhibitors, represented by Kobe0065, that displayed anti-proliferative activity on xenografts of human colorectal cancer (CRC) cell line SW480 carrying the K-ras(G12V) gene. Here we show that treatment of cancer cells carrying the activated ras genes with Kobe0065 or a siRNA targeting Ras downregulates the expression of lysyl oxidase (LOX), which has been implicated in metastasis. LOX expression is enhanced by co-expression of Ras(G12V) through activation of phosphatidylinositol 3-kinase (PI3K)/Akt and concomitant accumulation of hypoxia-inducible factor (HIF)-1α. Furthermore, Kobe0065 effectively inhibits not only migration and invasion of cancer cells carrying the activated ras genes but also lung metastasis of human CRC cell line SW620 carrying the K-ras(G12V) gene. Collectively, these results indicate that Kobe0065 prevents metastasis through inhibition of the Ras-P13K-Akt-HIF-1α-LOX signaling and suggest that Ras inhibitors in general might exhibit both anti-proliferative and anti-metastatic properties toward cancer cells carrying the activated ras genes.

We report a 69-year-old female patient with advanced lung cancer who developed myocarditis concomitant with myasthenia gravis (MG), also known as “Herzmyasthenie,” after 3 cycles of nivolumab administration. Her initial symptoms were general malaise and double vision. However, her myocarditis deteriorated rapidly the following day, necessitating a temporary pacemaker and noninvasive positive pressure ventilation in the intensive care unit. Immunohistochemical examination of a myocardial biopsy suggested an immune response on the basis of HLA associations. The patient also developed impaired adduction of her left eye and elevated serum levels of acetylcholine receptor antibody, suggesting the onset of MG. Her condition gradually improved after immediate methylprednisolone pulse therapy. This case of nivolumab-induced “Herzmyasthenie” highlights the need to be aware that fulminant myocarditis might occur at the same time as MG during treatment with anti-programmed cell death-1 monoclonal antibodies.

Key Clinical Message We present a lymphoplasmacytic lymphoma patient with Factor X (FX) deficiency. Despite the absence of FX inhibitor, the administration of fresh frozen plasma and anti‐inhibitor coagulant complex did not increase the FX level. The autopsy showed that massive amyloid depositions to multiple organs and FX existed in union with amyloidosis.

Several recent clinical and epidemiological studies have suggested inhibitory effects of light-to-moderate alcohol consumption on nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH); however, these effects have not been confirmed in experimental studies. Therefore, in this study, we examined the effects of small amounts of ethanol consumption on a mouse model of NASH. Nine-week-old male obese mice (db/db mice) were divided into the following groups: control, high-fat, and low-ethanol groups. The control group was provided ad libitum access to a control liquid diet, the high-fat group was provided access to a high-fat liquid diet, and the low-ethanol group was provided access to the high-fat liquid diet supplemented with 0.1% (w/w) ethanol. Eight weeks later, the mice were sacrificed and serum biochemical, histopathological, and molecular analyses were performed. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were significantly lower in the low-ethanol group than in the high-fat group (p = 0.033 and 0.037, respectively). Liver histopathological analysis showed that intralobular and portal inflammation was significantly milder in the low-ethanol group than in the high-fat group (p = 0.018 and 0.041, respectively). However, no significant differences were observed among the groups in serum insulin and adiponectin levels, hepatic 4-hydroxynonenal (oxidative injury marker) levels, and hepatic cytokine and receptor gene expression levels. In conclusion, the serum transaminase levels and hepatic inflammation in NASH model mice improved after administration of small amounts of ethanol. This study directly demonstrated inhibitory effects of small amounts of ethanol on NASH in mice. The mechanisms underlying these inhibitory effects remain to be elucidated.

Although radiological diagnostics have been progressing, pathological diagnosis remains the most reliable method for diagnosing liver tumors. In some cases, definite pathological diagnosis cannot be obtained by histological evaluation alone, especially when the sample is a small biopsy; in such cases, immunohistochemical staining is very useful. Immunohistochemistry is the most frequently used technique for molecular pathological diagnosis due to its broad application, ease of performance and evaluation, and reasonable cost. The results occasionally reflect specific genetic mutations. The immunohistochemical markers of hepatocellular carcinoma include those of hepatocellular differentiation—such as hepatocyte paraffin 1 and arginase-1—and those of malignant hepatocytes—such as glypican-3, heat shock protein 70, and glutamine synthetase (GS). To classify the subtypes of hepatocellular adenoma, examination of several immunohistochemical markers, such as liver fatty acid-binding protein, GS, and serum amyloid A, is indispensable. Immunohistochemical staining for GS is also important for the diagnosis of focal nodular hyperplasia. The representative immunohistochemical markers of intrahepatic cholangiocarcinoma include cytokeratin (CK) 7 and CK19. In this article, we provide an overview of the application of immunohistochemistry in the pathological diagnosis of liver tumors referring to the association with genetic alterations. Furthermore, we aimed to explain the practical points in the differential diagnosis of liver tumors by immunohistochemical staining.

The patient was a 70-year-old man. He was diagnosed with advanced transverse colon cancer. A computed tomography (CT)revealed liver metastasis and tumor thrombosis of portal vein. We started combination chemotherapy with capecita- bine/oxaliplatin(CapeOX). Perforation of the tumor was observed 5 days after CapeOX therapy was started. Treatment with abscess drainage and ileostmy, infection was controlled and general condition was improved. After 9 courses of CapeOX, we changed chemotherapy regimen to irinotecan/tegafur-gimeracil-oteracilpotassium (IRIS)due to strong side effects. In CT and FDG-PET examination after 8 courses of IRIS, the tumor of transverse colon, liver metastasis, and the tumor thrombosis of portalvein became unclear. A year and 6 months have passed since chemotherapy was started, recurrence was not observed. For the patients with unresectable colorectal cancer, it is necessary to consider multidisciplinary treatments including chemotherapy while considering the general condition of them.

We report 4 patients with occult breast cancer(OBC)who underwent breast conserving therapy(BCT)after neoadjuvant chemotherapy(NAC). All patients complained of axillary tumor and were diagnosed by core needle biopsy. Pathological examination of the axillary lymph nodes proved that 3 cases were adenocarcinomas and 1 case was squamous cell carcinoma, but imaging studies could not depict any primary lesions in the breast and other organs. Since distant metastasis was not observed, BCT with axillary lymph node dissection(ALND)was performed after NAC. All patients were undergoing whole breast irradiation. There were no residual cancer cells in the axillary lymph nodes in case 1 due to the treatment effect of NAC, but lymph node metastasis remained in other 3 cases. In the second case, she followed a rapid outcome, and pulmonary metastasis appeared in 7 months after surgery and died in 10 months. In the other 3 cases, there has not been found local and distant recurrence. Although OBC requires appropriate systemic treatment, present observation indicated that ALND with breast irradiation after NAC could be a useful option.

Aim Recent studies have indicated that hepatocellular adenoma (HCA) is a heterogenous group of benign tumors with various genetic and clinicopathological characteristics. We delineated the clinicopathological characteristics of HCA subtypes and evaluated the expression of transporter protein OATP1B3 in HCA. Methods HCA in 34 Japanese patients were investigated immunohistochemically and classified into four subtypes (HNF1α-inactivated type, H-HCA; β-catenin-activated type, b-HCA; inflammatory type, I-HCA; unclassified type, u-HCA). Immunostaining of OATP1B3 protein in HCA tissue sections was performed to determine the association between OATP1B3 expression and HCA subtypes. Results HCA was categorized into the following four subtypes and two combined subtypes: 10 H-HCA (29%), 10 I-HCA (29%), seven b-HCA (21%), two b-HCA/H-HCA (6%), two b-HCA/I-HCA (6%) and three u-HCA (9%). The male-to-female ratio was 18:16. Oral contraceptive use was rare but seven HCA were found in patients with glycogen storage disease, congenital absence of the portal vein and idiopathic portal hypertension. OATP1B3 expression was decreased in 24 HCA but was preserved or increased in 10 HCA. All nine HCA with nuclear staining for β-catenin showed preserved or enhanced OATP1B3 expression, indicating a significant association between nuclear β-catenin accumulation and OATP1B3 expression in HCA. Conclusion HCA subtype classification was validated in 91% of our Japanese subjects although their clinical backgrounds including rare contraceptive use were different from European subjects. A close association between preserved or enhanced OATP1B3 expression and b-HCA subtype indicated important modalities for clinical decisions in the treatment and follow up of patients with HCA.

Few studies have investigated the effects of Japanese herbal medicines on nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). To the best of our knowledge, only one study has examined whether high-fat (HF) diet-fed db/db mice are appropriate animal models of NASH. We investigated the effects of four types of Japanese herbal medicines (shosaikoto (TJ-9), inchinkoto (TJ-135), juzentaihoto (TJ-48), and keishibukuryogan (TJ-25)) on hepatic lesions of HF diet-fed db/db mice. Db/db mice were divided into six groups: control diet (control); HF diet (HF); and HF diet supplemented with TJ-9, TJ-135, TJ-48, or TJ-25 (TJ-9, TJ-135, TJ-48, and TJ-25, respectively). Mice were killed after 6 weeks of treatment, and biochemical and pathological analyses were performed. Mice in the HF group consistently developed histopathological features consistent with definite NASH, and marked necroinflammation occurred. Serum alanine aminotransferase levels in the TJ-9, TJ-135, and TJ-48 groups were significantly improved compared with those in the HF group. With regard to liver histology, TJ-9 and TJ-48 significantly improved lobular inflammation, and TJ-135 significantly improved ballooning degeneration. We have shown that HF diet-fed db/db mice are animal models that correctly recapitulate the histopathology of human NASH and that TJ-9, TJ-135, and TJ-48 inhibit necroinflammatory activity in this model.

A lipomatous ganglioneuroma is a rare variant of a ganglioneuroma. This case study describes a primary retroperitoneal lipomatous ganglioneuroma discovered in the course of our clinical work. The case involved a 50-year-old male. The patient was referred to our hospital for tumor resection. Computed tomography (CT) and magnetic resonance imaging revealed an imaging of 8 cm tumor adhering to the left renal artery. We constructed a three-dimensional organ model with a three-dimensional printer according to CT data and, upon confirming strong adhesion to the renal artery and kidney, performed a laparoscopic radical nephrectomy of the left kidney. The mass was diagnosed as a lipomatous ganglioneuroma by pathological assessment including immunohistochemistry. This is the third known report of a retroperitoneal lipomatous ganglioneuroma. This case allowed us to experience an extremely rare lipomatous ganglioneuroma.

The estrogen receptor (ER) is a key molecule for growth of breast cancers. It has been a successful target for treatment of breast cancers. Elucidation of the ER expression mechanism is of importance for designing therapeutics for ER-positive breast cancers. However, the detailed mechanism of ER stability is still unclear. Here, we report that histone acetyltransferase Hbo1 promotes destabilization of estrogen receptor α (ERα) in breast cancers through lysine 48-linked ubiquitination. The acetyltransferase activity of Hbo1 is linked to its activity for ERα ubiquitination. Depletion of Hbo1 and anti-estrogen treatment displayed a potent growth suppression of breast cancer cell line. Hbo1 modulated transcription by ERα. Mutually exclusive expression of Hbo1 and ERα was observed in roughly half of the human breast tumors examined in the present study. Modulation of ER stability by Hbo1 in breast cancers may provide a novel therapeutic possibility.

Aim In order to evaluate and judge a fibrotic stage of patients with chronic hepatitis C, multivariate regression analysis was performed using multiple fibrotic markers. Methods A total of 581 patients from eight hepatology units and institutes were diagnosed by needle biopsy as having chronic liver disease caused by hepatitis C virus. Twenty-three variables and their natural logarithmic transformation were employed in the multivariate analysis. Results Multivariate regression analysis finally obtained the following function: z = 2.89 × ln (type IV collagen 7S) (ng/mL) − 0.011 × (platelet count) (×103/mm3) + 0.79 × ln (total bilirubin) (mg/dL) + 0.39 × ln (hyaluronic acid) (μg/L) − 1.87. Median values of the fibrotic score of F1 (n = 172), F2 (n = 80), F3 (n = 37) and F4 (n = 16) were calculated as 1.00, 1.45, 2.82 and 3.83, respectively. Multiple regression coefficient and coefficient of determination were 0.56 and 0.320, respectively. Validation with patient data from other institutions demonstrated good reproducibility of the fibrotic score for hepatitis C (FSC), showing 1.10 in F1 (n = 156), 2.35 in F2 (n = 73), 3.16 in F3 (n = 36) and 3.58 in F4 (n = 11). Conclusion A concise multiple regression function using four laboratory parameters successfully predicted pathological fibrotic stage of patients with hepatitis C virus infection.

Background The purpose of this study is to investigate whether ordinary hepatocellular carcinomas (HCCs) show positivity of stem/progenitor cell markers and cholangiocyte markers during the process of tumor progression. Methods Ninety‐four HCC lesions no larger than 8 cm from 94 patients were immuno‐histochemically studied using two hepatocyte markers (Hep par 1 and α‐fetoprotein), five cholangiocyte markers (cytokeratin CK7, CK19, Muc1, epithelial membrane antigen and carcinoembryonic antigen) and three hepatic stem/progenitor cell markers (CD56, c‐Kit and EpCAM). The tumors were classified into three groups by tumor size: S1, < 2.0 cm; S2, 2.0–5.0 cm; S3, 5.0–8.0 cm. The tumors were also classified according to tumor differentiation: well, moderately and poorly differentiated. The relationship between the positive ratios of these markers, tumor size and tumor differentiation was examined. Results The positive ratios of cholangiocyte markers tended to be higher in larger sized and more poorly differentiated tumors (except for CK7). The positive ratios of stem/progenitor cell markers tended to be higher in larger sized and more poorly differentiated tumors (except for c‐Kit). Conclusion Ordinary HCC can acquire the characteristic of positivity of cholangiocyte and stem/progenitor cell markers during the process of tumor progression.

Aims/Introduction: The computed tomography (CT) value of the pancreas was examined across the range of glucose tolerance, and the relationships between pancreatic CT values and factors responsible for glucose intolerance were analyzed. Materials and Methods: A total of 167 health-check examinees were classified into normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes mellitus (DM) according to 75 g oral glucose tolerance test (OGTT). Pancreatic and hepatic CT values were estimated at decreasing stages of glucose tolerance. The association of CT values of the pancreas and the indices of glucose tolerance were analyzed. Results: Insulinogenic index (II) was decreased from NGT through IGT to DM. Mean pancreatic CT value was decreased significantly from NGT through IGT to DM. Mean area under the curves of glucose (AUC-G) was significantly associated with II and insulin sensitivity index (ISI) composite in univariate analysis. In multiple regression analysis, II was most strongly inversely correlated with mean AUC-G, suggesting that II is the strongest determinant of glucose tolerance in Japanese. In addition, II was significantly associated with mean pancreatic CT value in univariate analysis. In multiple regression analysis, mean pancreatic CT value was strongly correlated with II. Conclusions: Pancreatic CT values were significantly decreased from NGT through IGT to DM. II was the strongest determinant of glucose tolerance, and was significantly influenced by pancreatic CT values. Thus, pancreatic fat deposition might impair insulin secretion in the early stage of development of type 2 diabetes, before overt deterioration of glucose tolerance. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00212.x, 2012)

Aim: Non-alcoholic steatohepatitis (NASH) has been classified pathologically into type 1 (characterized by ballooning and perisinusoidal fibrosis) and type 2 (characterized by portal inflammation and portal fibrosis). Reportedly, type 2 NASH has been the most commonly observed histopathological feature in pediatric non-alcoholic fatty liver disease (NAFLD). While only a few studies have documented the histopathology of pediatric NAFLD so far, appropriate histopathological classification or characteristics of pediatric NAFLD, and the disease incidence correlation with race or ethnicity are still controversial. Methods: In this study, we compared the clinical and histopathological characteristics of NAFLD in 34 pediatric and 23 adult cases. Results: We found that pediatric steatosis was more severe than adult steatosis. Perisinusoidal fibrosis was significantly milder in pediatric cases than in adult cases. Lobular inflammation and ballooning was found to be milder in pediatric cases than in adult cases. On the other hand, portal inflammation was more severe in pediatric cases than in adult cases. The so-called borderline zone 1 NASH, similar to type 2 NASH, was observed in 21% of pediatric subjects; this rate was more than twice that in adult subjects. Fifty percent of pediatric cases showed overlapping features of types 1 and 2 NASH. Intralobular and portal changes showed positive and significant correlations with each other. Serum aminotransferase levels reflected the histopathological severity of NAFLD. Conclusion: We confirmed that pediatric NAFLD exhibits histopathological features that are different from adult NAFLD. The classification consisting of “type 1 NASH” and “type 2 NASH” may be impractical.

Purpose: To describe the clinical and genetic characteristics of a Japanese family in which one member exhibited Bietti’s crystalline corneoretinal dystrophy (BCD). Methods: Using direct sequencing, mutation screening was performed in the CYP4V2 gene of both the patient with BCD and her daughter. Ophthalmic examinations were performed to determine the clinical features of both subjects. Results: The 64-year-old female patient had a bilateral visual acuity of 0.4. Slit lamp examination revealed bilateral crystalline-like deposits at the superior limbus of the cornea. Fundus examination revealed there was chorioretinal atrophy along with numerous glistening yellowish-white crystalline deposits that were scattered throughout the posterior pole and the mid-peripheral retina. Standard flash electroretinography showed an extinguished electroretinogram and Goldmann kinetic perimetry detected a relative scotoma. Genetic analysis revealed that the patient had a heterozygous mutation in the CYP4V2 gene (IVS6–8delTCATACAGGTCATCGCG/GC), which is the most commonly found mutation in Japanese patients with BCD. Furthermore, the patient was also shown to have a novel heterozygous point mutation in exon 9 of the CYP4V2 gene (c.1168C>T). In contrast, her daughter exhibited no clinical findings for BCD even though she carried the same heterozygous mutation in the CYP4V2 gene (c.1168C>T).