Two Japanese Families with Pigmented Paravenous Retinochoroidal Atrophy and HK1 Mutation: A Case Report.

Hexokinase 1 (HK1) gene is the cause of autosomal dominant retinitis pigmentosa (RP) 79. To date, only E874K mutation has been reported as the causative mutation in patients with nonsyndromic RP. As a Caucasian RP case with a pathological variant of HK1 exhibiting pigmented paravenous retinochoroidal atrophy (PPRCA) phenotype was recently reported, we reviewed RP79 cases in our Japanese RP cohort. Consequently, 2 Japanese patients, who were diagnosed with RP79 by genetic tests in our RP cohort, were included in this study. Patient 1 was a 60-year-old woman. Fundus examination revealed symmetrical donut-shaped retinal degeneration, with pigment deposition avoiding the macula. Moreover, degeneration extended in a peripheral direction along the vessels like a starfish, and degeneration was observed around the veins and arteries. Patient 2 was a 75-year-old man. Fundus examination revealed symmetric macula-avoiding donut-shaped retinal degeneration, with paravenous protruding degeneration along the blood vessels like in case 1. Both Japanese cases, which belonged to two separate families, had the same HK1 pathogenic mutation, with a phenotype of PPRCA. Furthermore, atrophy along retinal arteries was noted. Reviewing previous nonsyndromic RP79 cases revealed symptoms that are believed to be those of PPRCA. Ultra-widefield fundus imaging, especially ultra-widefield fundus autofluorescence, has been useful in detecting PPRCA. If these devices become widely available, more cases may be discovered in the future because PPRCA can be used as a clue to suspect RP79, and Sanger sequencing may be used to identify pathogenic mutations in HK1 at a lower cost and more easily than using whole-exome sequencing.

Comparison of the specimen quality of endobronchial ultrasound-guided intranodal forceps biopsy using standard-sized forceps versus mini forceps for lung cancer: A prospective study.

BACKGROUND AND OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a diagnostic procedure with adequate performance; however, its ability to provide specimens of sufficient quality and quantity for treatment decision-making in advanced-stage lung cancer may be limited, primarily due to blood contamination. The use of a 0.96-mm miniforceps biopsy (MFB) permits true histological sampling, but the resulting small specimens are unsuitable for the intended applications. Therefore, we introduced a 1.9-mm standard-sized forceps biopsy (SFB) and compared its utility to that of MFB. METHODS: We prospectively enrolled patients from three institutions who presented with hilar/mediastinal lymphadenopathy and suspected advanced-stage lung cancer, or those who were already diagnosed but required additional tissue specimens for biomarker analysis. Each patient underwent MFB followed by SFB three or four times through the tract created by TBNA using a 22-gauge needle on the same lymph node (LN). Two pathologists assessed the quality and size of each specimen using a virtual slide system, and diagnostic performance was compared between the MFB and SFB groups. RESULTS: Among the 60 enrolled patients, 70.0% were diagnosed with adenocarcinoma. The most frequently targeted sites were the lower paratracheal LNs, followed by the interlobar LNs. The diagnostic yields of TBNA, MFB and SFB were 91.7%, 93.3% and 96.7%, respectively. The sampling rate of high-quality specimens was significantly higher in the SFB group. Moreover, the mean specimen size for SFB was three times larger than for MFB. CONCLUSION: SFB is useful for obtaining sufficient qualitative and quantitative specimens.

Intestinal­type mucinous carcinoma of the endometrium showing a polypoidal exophytic form: A case report.

Although endometrial cancer is a common malignancy in women, rare histological subtypes can pose diagnostic challenges. Primary endometrial intestinal-type mucinous carcinoma is a newly recognized subtype of endometrial cancer that differs from Müllerian-type endometrial mucinous carcinoma. The present case report documents a rare case of intestinal-type mucinous carcinoma of the endometrium showing a polypoidal exophytic form. The patient, an 80-year-old female, was incidentally diagnosed with a uterine tumor during a follow-up for vulvar Paget's disease. Clinical and imaging examinations revealed a localized mass within the uterine cavity. Hysteroscopy and subsequent histological examination confirmed the presence of intestinal-type mucinous carcinoma of the endometrium. Microscopically, the tumor displayed adenocarcinoma containing an intestinal-type glandular epithelium with mild nuclear atypia. It stained positive for the gastrointestinal markers mucin 2 and caudal type homeobox 2, and stained negatively for estrogen receptor α. The patient underwent surgery and adjuvant chemotherapy, with no evidence of recurrence at the latest follow-up 6 months after surgery. Endometrial intestinal-type mucinous carcinoma is a rare histological subtype of endometrial cancer. Differential diagnoses include Müllerian-type endometrial mucinous carcinoma, endocervical adenocarcinoma, metastasis from gastrointestinal tract adenocarcinoma and non-neoplastic gastric/intestinal metaplasia. However, the prognosis of endometrial intestinal-type mucinous carcinoma remains unclear due to limited reported cases. Existing evidence suggests a poorer prognosis compared with classical mucinous carcinomas of the endometrium. The present case, which is characterized by a polypoidal exophytic tumor without myometrial invasion, showed a favorable outcome. Further documentation and characterization of the aforementioned rare malignancy are necessary to enhance the understanding of its clinical physiology and outcomes. The present case report highlights the diagnostic challenges associated with intestinal-type mucinous endometrial carcinoma. The inclusion of this type of malignancy in the latest World Health Organization classification emphasizes the need for further comprehensive studies and case reports to expand the current knowledge on this rare histological subtype.

Sinusoidal obstruction syndrome associated with disseminated toxoplasmosis involving the liver after allogeneic hematopoietic stem cell transplantation: A case report.

Sinusoidal obstruction syndrome (SOS) is a fatal complication after hematopoietic stem cell transplantation (HSCT). Only a few complications after HSCT have been reported as risk factors for SOS, including sepsis. Here, we report the case of a 35-year-old male diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia who underwent peripheral blood HSCT from a human leukocyte antigen-matched unrelated female donor in remission. Graft-versus-host disease prophylaxis contained tacrolimus, methotrexate, and low-dose anti-thymoglobulin. The patient was treated with methylprednisolone for engraftment syndrome from day 22. On day 53, he presented worsening fatigue, breathlessness, and abdominal pain in the right upper quadrant that had persisted for 4 days. Laboratory tests showed severe inflammation, liver dysfunction, and positive for Toxoplasma gondii PCR. He died on day 55. An autopsy showed SOS and disseminated toxoplasmosis. Hepatic infection with T. gondii was identified in zone 3 of the liver, which overlapped with the pathological features of SOS. In addition, the timing of the exacerbation of hepatic dysfunction coincided with the onset of systemic inflammatory symptoms and T. gondii reactivation. This rare case of toxoplasmosis is the first to suggest that hepatic infection with T. gondii is strongly associated with SOS after HSCT.

Ibrutinib Induces a Dramatic Improvement for Idiopathic Refractory Ascites Following Allogeneic Hematopoietic Cell Transplantation.

We herein report a case of idiopathic refractory ascites following allogeneic hematopoietic cell transplantation that was successfully treated with ibrutinib. A 39-year-old man presented with massive transudative ascites. Despite a high portal venous pressure, the liver histology showed traces of alloreactivity inconsistent with veno-occlusive disease/sinusoidal obstructive syndrome. Ibrutinib was administered for ascites possibly secondary to portal hypertension associated with the alloreactivity. The ascites dramatically improved, and the portal venous pressure was reduced. This case may help clarify the mechanism through which refractory ascites develops after allogeneic hematopoietic cell transplantation and establish appropriate treatment protocols.

Two cases of eosinophilic gastrointestinal disorder due to newly appearing food allergies after cord blood transplantation.

Eosinophilic gastrointestinal disorders (EGIDs) are infrequent complications after allogeneic hematopoietic cell transplantation (allo-HCT). Furthermore, it is well-known that allergic diseases are transferable after allo-HCT from allergic donors to non-allergic recipients. However, the type of graft-versus host disease (GVHD) prophylaxis that leads to allergic disease transfer is unclear. Furthermore, no study has reported a case of acquired food allergy resulting in EGID that was detected based on the clinical course and the detection of antigen-specific immunoglobulin E after allo-HCT. We encountered two patients with acute leukemia accompanied by eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE) due to newly appearing food allergy after cord blood transplantation (CBT) with T-cell non-depletion GVHD prophylaxis. Despite having no history of allergic disease, the patients experienced allergic symptoms due to dairy products (Case 1) and eggs (Case 2) after CBT. They subsequently experienced severe nausea, heartburn, and anorexia (Case 1) and diarrhea (Case 2). Cases 1 and 2 were diagnosed with EoE and EGE, respectively, based on endoscopic and histological examinations. Dietary treatment without steroids improved the symptoms in both cases. These cases highlight that the unexpected transfer of food allergy after CBT can lead to EGIDs, especially in patients receiving T-cell non-depletion GVHD prophylaxis.

Impact of long-term optimizing atrioventricular delay using device-based algorithms on cardiac resynchronization therapy.

Sub-optimal atrioventricular delay (AVD) is one of the main causes of non-responder for cardiac resynchronization therapy (CRT). Recently, device-based algorithms (DBAs) that provide optimal AVD based on intracardiac electrograms, have been developed. However, their long-term effectiveness is still unknown. This study aims to investigate the effect of optimizing AVD using DBAs over a long period, on the prognosis of patients undergoing CRT. A total of 118 patients who underwent CRT at our hospital between April 2008 and March 2018, were retrospectively reviewed; 61 of them with optimizing AVD using DBAs were classified into the treated group (group 1), and the remaining 57 were classified into the control group (group 2). The median follow-up period was 46.0 months. The responder and survival rate in group 1 were significantly better than those in group 2 (group 1 vs. group 2: responder rate = 64% vs. 46%, p = 0.046; survival rate: 85.2% vs. 64.9%, p = 0.02). Moreover, investigating only the non-responder population showed that group 1 had an improved survival rate compared to group 2 (group 1 vs. group 2 = 72.7% vs. 45.1%, p = 0.02). Optimizing AVD using DBAs was a significant contributor to the improved survival rate in CRT non-responders in multivariate analysis (HR 3.6, p = 0.01). In conclusion, the long-term optimizing AVD using DBAs improved the survival rate in CRT and the prognosis of CRT non-responders, as well.

Preliminary Outcomes of Cervical Cerclage for Shortened Cervix with Decidual Polyp.

The aim of this study was to elucidate the nature of decidual polyp (DP) and to compare DP outcomes treated with cervical cerclage for a shortened cervix with the outcomes of cases treated with cervical cerclage without DP. The medical records of pregnant women who were complicated with cervical polyps were retrospectively reviewed. Cervical cerclage was considered for those cases with a shortened cervical length of under 25 mm and before 25 gestational weeks. We also reviewed pregnant women who had no cervical polyps, and who underwent cervical cerclage during the same study period, and defined them as the control group. A total of 56 pregnant women with cervical polyps were identified. All of the polyps in the 14 cases that had undergone cervical cerclage migrated into the cervical canal. Of the thirty seven cases with cervical polyps that did not necessitate cervical cerclage, eight women delivered preterm and six of these cases were diagnosed as DP. In all of the women studied, polyp migration was observed in 68.6 %. Cervical cerclage was performed significantly earlier in the DP group than in the control group of 46 cases (p < 0.001; 18.4 weeks vs. 21.4 weeks, respectively). Cervical cerclage is effective in DP cases with a shortened cervical length and polypectomy should not be performed during pregnancy because of the risk of miscarriage.

Upper arm posture during human embryonic and fetal development.

The upper extremity posture is characteristic of each Carnegie stage (CS), particularly between CS18 and CS23. Morphogenesis of the shoulder joint complex largely contributes to posture, although the exact position of the shoulder joints has not been described. In the present study, the position of the upper arm was first quantitatively measured, and the contribution of the position of the shoulder girdle, including the scapula and glenohumeral (GH) joint, was then evaluated. Twenty-nine human fetal specimens from the Kyoto Collection were used in this study. The morphogenesis and three-dimensional position of the shoulder girdle and humerus were analyzed using phase-contrast X-ray computed tomography and magnetic resonance imaging. Both abduction and flexion of the upper arm displayed a local maximum at CS20. Abduction gradually decreased until the middle fetal period, which was a prominent feature. Flexion was less than 90° at the local maximum, which was discrepant between appearance and measurement value in our study. The scapular body exhibited a unique position, being oriented internally and in the upward direction, with the glenoid cavity oriented cranially and ventrally. However, this unique scapular position had little effect on the upper arm posture because the angle of the scapula on the thorax was canceled as the angle of the GH joint had changed to a mirror image of that angle. Our present study suggested that measuring the angle of the scapula on the thorax and that of the GH joint using sonography leads to improved staging of the human embryo.

Extensive Macular Atrophy with Pseudodrusen in a Japanese Patient Evaluated by Wide-Field OCTA.

Extensive macular atrophy with pseudodrusen (EMAP) is a relatively newly proposed clinical entity that was first reported in 2009. Although no definitive diagnostic criteria have been defined, characteristic findings can distinguish it from other diseases, especially dry age-related macular dystrophy (AMD). Herein, we present the case of a patient with EMAP who underwent a comprehensive ophthalmic examination and whole-exome sequencing (WES). A 72-year-old Japanese man complained of progressive visual impairment in his right eye and nyctalopia. Ophthalmic examination revealed that the best-corrected visual acuity (BCVA) in decimal units was 0.08 on the right and 0.8 on the left. Fundoscopy and fundus autofluorescence (FAF) revealed well-demarcated symmetrical macular atrophy, with a vertical axis larger than the horizontal axis, which reached the vascular arcade inferiorly and exceeded it superiorly. Pseudodrusen were widespread throughout the retina in both eyes. Paving-stone degeneration was not observed in the extreme periphery of either eye. Seven months later, his left BCVA decreased to 0.3 without major changes on multimodal imaging. Based on the above findings, we diagnosed EMAP. Wide-field optical coherence tomography angiography (OCTA) showed no significant changes in the retinal vessels, but the density of choroidal vessels was reduced in the degenerated areas. We thought that this finding suggests that EMAP originates between the deep retina and choroid. WES did not reveal any candidate mutations in known pathogenic genes. To the best of our knowledge, this is the first report of a Japanese patient with EMAP, and no data for analysis of wide-field OCTA or equatorial OCT images of EMAP cases have been found in previous reports. EMAP is not well recognized in Asia and may be incorrectly diagnosed as dry-type AMD. EMAP should be included in the differential diagnosis of dry AMD, and this may lead to more Asians being diagnosed with EMAP in the future.

IgG4-related mastitis requiring differentiation from breast cancer: a case report.

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a group of chronic relapsing inflammatory conditions. Although IgG4-RD can occur in various organs, it is rarely observed in mammary glands. Here, we report a case of IgG4-related mastitis (IgG4-RM) that needed to be differentiated from breast cancer. A 54-year-old woman was examined for a tumor in her left breast. Mammary ultrasonography revealed an irregular hypoechoic tumor measuring 45.0 × 43.0 × 32.0 mm in size. A core-needle biopsy of the left breast tissue revealed a high degree of mixed T and B lymphocytic and plasma cell infiltration, as well as interstitial fibrosis. IgG4-RD was diagnosed based on hematological examination that revealed an abnormal IgG4 value of 332 mg/dl. All the clinical diagnostic criteria for IgG4 were met, resulting in a definitive diagnosis of IgG4-RM.

Breast Angiosarcoma with a Preoperative Diagnosis of Late Recurrence of Breast Cancer: A Case Report.

Angiosarcoma is a malignant mesenchymal tumor characterized by the presence of vascular endothelial cells. Although rare, angiosarcoma developing in the mammary glands has a poor prognosis. We report a case of breast angiosarcoma with a preoperative diagnosis of late recurrence of breast cancer. A 78-year-old woman noticed a tumor in her right breast and visited our hospital. The patient had undergone breast-conserving surgery and axillary lymph node dissection from the right breast 12 years before the visit. The tumor was diagnosed as T4bN0M0, stage IIIB. Anastrozole was administered as postoperative adjuvant therapy for 5 years; the patient also received 50-Gy whole-breast radiation therapy after surgery. Physical examination during her visit revealed an elevated lesion with blue purpura around the nipple in the right breast. We performed breast ultrasound and detected a well-defined 19.6 × 16.4 × 10.7 mm hypoechoic tumor in the left subareolar area. The patient underwent core needle biopsy (CNB). Based on the CNB specimen findings, she was suspected to experience late local recurrence after surgery. Therefore, she underwent total mastectomy after breast-conserving surgery. A dark-red tumor sized 18 × 12 mm was found in a specimen from the nipple. The pathological diagnosis of the specimen revealed short spindle-shaped tumor cells with strong nuclear pleomorphism and a significant interstitial fibrosis. Immunohistochemistry using D2-40 and CD31 antibodies showed irregular luminal proliferation at the anastomosis, infiltration into the surrounding tissue, and massive necrosis, thereby leading to the diagnosis of breast angiosarcoma. We have reported a case of breast angiosarcoma with a preoperative diagnosis of late recurrence of breast cancer.

HbA1c levels Measured by Enzymatic Assay and Immunoassay during Off-Site Health Checkups Are Both Lower than Those Measured by On-Site HPLC Assay.

It has already been reported that HbA1c levels measured by immunoassay (IA) (IA-HbA1c) during off-site health checkups present falsely lower results. We also reported that HbA1c levels measured by enzymatic assay (EA) (EA-HbA1c) during off-site health checkups are lower. In the present study, we compared IA-HbA1c levels or EA-HbA1c levels during off-site health checkups with on-site high-performance liquid chromatography (HPLC)-HbA1c levels using the same samples. Subjects were 88 non-diabetic individuals who had health checkups in Nishinomiya Municipal Central Hospital. Subjects with a history of diabetes mellitus and those with HPLC-HbA1c ≥ 6.5% were excluded. IA-HbA1c levels (Study 1) or EA-HbA1c levels (Study 2) in the health checkups were compared with on-site HPLC-HbA1c levels using the same samples. Both IA-HbA1c levels and EA-HbA1c levels had positive correlations with HPLC-HbA1c levels (p <0.0001 for both), although both were significantly lower than HPLC-HbA1c levels (p <0.0001 for both). The degrees of reductions in the IA-HbA1c levels and EA-HbA1c levels compared with HPLC-HbA1c levels were almost same to each other. Similarly to IA-HbA1c levels, EA-HbA1c levels during the health checkups were lower than HPLC-HbA1c levels. It was demonstrated that HbA1c levels decrease similarly if measured by either EA or IA during off-site health checkups.

Transvenous lead performance of implantable cardioverter-defibrillators and pacemakers.

BACKGROUND: After the reports of recalled leads, several technological improvements have been introduced and the durability of implantable cardioverter defibrillator (ICD) leads has improved. The incidence of lead failures is now less than in the previous studies. However, there are few reports that have shown the long-term durability of ICD leads as compared to pacemaker (PM) leads. This study analyzed the medium to long-term performance of transvenous ICD leads as compared to PM leads. METHODS: We retrospectively studied 1227 cases from April 2007 to December 2017 who underwent an initial transvenous ICD or PM implantation. The number of lead failures and patient background characteristics were analyzed. RESULTS: During a median 3-3.5 years follow up period, 1 (0.3%) ICD lead and 18 (2.4%) PM leads failed. The incidence of lead failures was significantly higher in the PM group than ICD group (p = .019). Males were associated with a higher incidence of lead failures in the PM group. CONCLUSION: Since the era of recalled ICD leads, the durability of ICD leads has remarkably improved and the incidence of lead failures with non-recalled ICD leads has been less than that for PM leads.

Impact of high-density mapping on outcome of the second ablation for atrial fibrillation.

PURPOSE: Identification of a conduction gap between the left atrium and pulmonary vein (LA-PV gap) and the circuit of atrial tachycardia after pulmonary vein isolation (PVI) is an important process during the second ablation for atrial fibrillation (AF). The high-density mapping system RHYTHMIA® is useful for identification of an LA-PV gap and the circuit of atrial tachycardia. Therefore, this study was performed to investigate the effect of RHYTHMIA® in terms of the outcome of the second ablation for AF. METHODS: One hundred patients underwent a second ablation for AF in our institute from April 2015 to December 2018. We retrospectively evaluated 49 patients using RHYTHMIA® (group 1) and 51 patients using the conventional method with additional anatomical guide by CARTO® system. RESULTS: In group 1, we performed redo PVI for 41 patients with 49 LA-PV countable gaps and ablation for other atrial arrhythmias in 7 patients. In group 2, we performed redo PVI in 40 patients with 33 LA-PV countable gaps and ablation for other atrial arrhythmias in 9 patients. Three and two unstable arrhythmias in each group were not ablated. The final recurrence of atrial arrhythmia was significantly lower in group 1 than 2 (8/49 (16%) vs. 17/51 (33%), respectively; P = 0.017). Atrial arrhythmias other than AF after the second ablation occurred in only one patient in group 1 but seven patients in group 2. CONCLUSION: Using high-density mapping for the second ablation of AF was found to be superior to the conventional ablation method in terms of the suppression of atrial events in this study. This technique warrants further investigation.

Shoulder girdle formation and positioning during embryonic and early fetal human development.

Positional information on the shoulder girdle (the clavicle and scapula) is important for a better understanding of the function of the upper limb in the locomotive system as well as its associated disease pathogenesis. However, such data are limited except for information on the axial position of the scapula. Here, we describe a three-dimensional reconstruction of the shoulder girdle including the clavicle and scapula, and its relationship to different landmarks in the body. Thirty-six human fetal specimens (crown-rump length range: 7.6-225 mm) from the Kyoto Collection were used for this study. The morphogenesis and three-dimensional position of the shoulder girdle were analyzed with phase-contrast X-ray computed tomography and magnetic resonance imaging. We first detected the scapula body along with the coracoid and humeral head at Carnegie stage 18; however, the connection between the body and coracoid was not confirmed at this stage. During development, all landmarks on the shoulder girdle remained at the same axial position except for the inferior angle, which implies that the scapula enlarged in the caudal direction and reached the adult axial position in the fetal period. The scapula body was rotated internally and in the upward direction at the initiation of morphogenesis, but in the fetal period the scapula body was different than that in the adult position. The shoulder girdle was located at the ventral side of the vertebrae at the time of initial morphogenesis, but changed its position to the lateral side of the vertebrae in the late embryonic and fetal periods. Such a unique position of the shoulder girdle may contribute to the stage-specific posture of the upper limb. Adequate internal and upward rotation of the scapula could help in reducing the shoulder width, thereby facilitating childbirth. The data presented in this study can be used as normal morphometric references for shoulder girdle evaluations in the embryonic and fetal periods.

Myopotential Oversensing Is a Major Cause of Inappropriate Shock in Subcutaneous Implantable Defibrillator in Japan.

Previous study has identified marked differences in patient characteristics and causes of inappropriate shock (IAS) between Japan and the Western societies in terms of subcutaneous implantable cardioverter-defibrillator (S-ICD). However, evidence of IAS in Asian populations including Japan has been limited to one observational study.Thus, we conducted a single-center registry study that tracks the postoperative course of 61 consecutive patients who received S-ICD from February 2016 to January 2020. Our findings showed that IAS occurred in 9.8% of the study population (6/61), which is comparable to the previously reported incidence. Remarkably, T-wave oversensing did not result in an IAS (0/6). Instead, myopotential oversensing was determined to have caused the most IAS events (4/6), while atrial fibrillation ranked second (2/6). A provocation maneuver (e.g., abdominal clench, push-ups, lifting a heavy item) reproduced myopotential noise disguised as R-waves, which should potentially trigger an IAS if uninterrupted. R-wave amplitude of the IAS group appeared relatively low compared to that of the non-IAS group although this finding was not tested significant. Furthermore, no temporal changes were noted in R-wave amplitude between the time of implantation and IAS events, suggesting that it is neither constantly low nor acutely dropped R-wave amplitude but a relatively high noise level that drives IAS. All the myopotential-IAS patients were found to be male. Right-sided lead implantation was associated with a higher incidence of IAS.This study highlights the fact that IAS continues to occur due to myopotential noise oversensing instead of T-wave oversensing. To minimize the risk of IAS, it is desirable to search and secure high R-wave voltage.

Novel mutation identified in Leber congenital amaurosis - a case report.

BACKGROUND: Leber congenital amaurosis (LCA) is the earliest onset and the most severe form of all inherited retinal degenerative disorders, characterized by blindness, or severe visual impairment from birth, and typically exhibits clinical and genetic heterogeneity. Recently, 14 causative genes of LCA were reported. We performed whole-exome sequencing (WES) for Japanese siblings, and identified a novel homozygous nonsense mutation in the RPGR-interacting protein 1 (RPGRIP1) gene. We also report their follow-up data over 27 years. CASE PRESENTATION: Patient 1 is a 37-year-old male. In 1992, his eye position indicated orthophoria, however, horizontal nystagmus was evident, and he complained of photophobia. His best corrected decimal visual acuity (BCVA) was 0.2 (S + 6.5/C-3.5/170°) OD and 0.1 (S + 6.0/C-2.5/10°) OS. Fundus examination revealed bisymmetrical inferior focal retinal pigment epithelium (RPE) mottling. Bright-flash electroretinogram (ERG) revealed a subnormal pattern, while 30 Hz flicker ERG was non-recordable in both eyes. At his final visit in 2019, his BCVA was 0.09 (S + 3.5/C-3.5/180°) OD and 0.09 (S + 3.0/C-4.0/10°) OS. Patient 2, a 34-year-old female, is the sibling of patient 1. In 1992, her BCVA was 0.05 (S + 6.0) OD and 0.06 (S + 5.0) OS. She was in a chin-up position during visual acuity testing. Horizontal nystagmus was evident, and she also complained of photophobia. Bright-flash ERG was severely attenuated, and 30 Hz flicker ERG was non-recordable in both eyes. At her final visit in 2019, her BCVA was 0.02 (uncorrectable) OD and 0.03 (uncorrectable) OS. There were no other patients with LCA in their family and their parents were non-consanguineous. WES revealed a homozygous, consecutive, two-nucleotide variation in the RPGRIP1 gene (NM_020366: exon15:c.G2294A and c.C2295A, p.C765X), resulting in a premature stop codon. We interpreted this variation as a novel pathogenic mutation of RPGRIP1 that contributes to LCA6 development. CONCLUSIONS: Herein, we report a novel nonsense mutation of RPGRIP1 in two patients with LCA6 and present their long-term follow-up data. These clinical data linked to genotypes provide important information for the development of new treatments, such as gene therapy, as well as for genetic counseling.