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Purpose: To explore the clinicopathological characteristics of immunoglobulin G4 (IgG4)-positive ocular adnexal marginal zone B-cell lymphoma (OAML) and associated patient treatment outcomes. Methods: Medical records from patients diagnosed with IgG4-positive OAML treated at the West China Hospital between January 2016 and August 2023 were retrospectively analyzed. Results: This study included data from 22 patients (11 males, 11 females), aged between 36 and 83 years, with disease durations from 1 month to 30 years. Sixteen cases exhibited unilateral ocular involvement (ten left eyes, six right eyes), while six exhibited bilateral involvement. Common clinical symptoms included ocular masses, eyelid swelling, and proptosis, with the orbit and lacrimal gland being the most commonly impacted sites. Among the 22 patients, 13 who were clinically suspected of having IgG4-related ophthalmic disease (IgG4-ROD) underwent serum IgG4 testing pre-operatively, revealing elevated IgG4 levels in 11 of these patients. The use of computed tomography and magnetic resonance imaging facilitated the evaluation of the location and size of lesions. All 22 patients received surgical treatment. Subsequently, 14 of these patients underwent local radiotherapy, five received post-operative chemotherapy, and three were closely observed. The follow-up period of patients in this study was 3–77 months, with an average follow-up time of 36 months. Except for one patient who died of disease progression, all others showed favorable prognoses with significant improvements. Conclusions: These results support the classification of IgG4-positive OAML as a distinct OAML sub-type with clinical features that partially overlap with IgG4-ROD. Therefore, accurate differentiation between OAML and IgG4-ROD is imperative, necessitating timely surgical intervention and precise pathological diagnosis to prevent diagnostic errors and inappropriate treatment. Currently, no standardized treatments for IgG4-positive OAML exist, but our results suggest that standard OAML therapies are generally efficacious.

Myeloid sarcoma (MS) occurs when primitive or naive myeloid cells form outside the bone marrow. It occurs mainly in soft/connective tissue and skin; orbital involvement is rare. We report the cases of two female adults, analyze the clinicopathologic characteristics, and review the literature. The average age of both patients was 28 years and they presented unilateral proptosis combined with varying degrees of impaired visual acuity and restricted ocular motility in the affected eye. Despite this, they maintained good overall health and no notable family history. However, the patients had no systemic clinical manifestations of acute myeloid leukemia (AML). Both patients underwent surgical resection of the orbital tumor. Immunohistochemistry showed positive staining for CD43, Leukocyte Common Antigen (LCA), and myeloperoxidase (MPO) and a high level of positive staining for Ki67, which were diagnostic for MS. Bone marrow cytology examination showed no apparent abnormalities. Postoperative chemotherapy, local radiotherapy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) were performed in Case 1, while the second patient underwent adjuvant chemotherapy and radiotherapy. No recurrence or metastasis was found in either patient during follow-up (one more than 5 years, the other more than 10 years). The occurrence of orbital MS is infrequent, with atypical clinical and imaging findings. The diagnosis depends on pathomorphology and immunohistochemical staining, and the prognosis is good with postoperative adjuvant chemotherapy, local radiotherapy, and allo-HSCT.

BackgroundSignificant individual differences exist in the clinical manifestations of thyroid-associated ophthalmopathy (TAO). Age and gender have an impact on the presentation and severity of TAO.ObjectiveTo evaluate the clinical characteristics of TAO patients, with particular consideration of their age and gender.MethodsDemographic and clinical data of 2479 TAO patients were collected. Patients were divided into 7 groups based on age: Group 1: ≤18 years old; Group 2: 19-29 years old; Group 3: 30-39 years old; Group 4: 40-49 years old; Group 5: 50-59 years old; Group 6: 60-69 years old; Group 7: ≥70 years old. Compared clinical manifestations among different groups and between males and females.ResultIn age group 1, the ratio of female to male TAO patients was 3.79, and in age group 7, it was 0.86. As age increased, there was a decline in the percentage of females (γ=-0.168, p

The Late Quaternary activity characteristics of secondary faults located between the main active faults at the boundaries of large basins are of great significance to the overall understanding of regional seismic hazards. The Wulashan Northern Fault (WNF) is located on the northern side of the Ordos Block, within the Northern Margin Fault Basin in North China, between the Sertengshan Piedmont Fault and Daqingshan Piedmont Fault. Current research on the geometry and kinematics of the WNF needs to be improved. In this study, we aimed to determine the shallow structural characteristics and Late Quaternary activity of the WNF using shallow seismic exploration and composite drilling geological cross-sectional analysis. The results indicate that the WNF is not a single surface fault but multiple branches with a northward-dipping stepped surface distribution. The latest activity of the F1 branch with a maximum coseismic vertical dislocation of 0.9 m occurred before 47.08 ± 3.7 ka B.P. The latest and older activities of the branch of F2 with a maximum coseismic vertical dislocation of 0.96 m and 1.15 m occurred before 73.8 ± 2.8 ka B.P. and 91.2 ± 4.4 ka B.P., respectively. According to a series of empirical relationships between length of surface rupture and magnitude, the maximum potential magnitude of the earthquake was determined to be M = 6.5–7.0. We argue that even though the Late Quaternary activity of the WNF was weaker than that of the other boundary faults of the Hetao Basin, the local urban and rural planning and land and resources construction in the Hetao Basin region should pay attention to the seismic risk of the WNF as an independent section in the future for the effect of secular tectonic loading.

Fungal orbital cellulitis is usually seen in immunocompromised individuals, and opportunistic pathogens are the main etiology. We herein report a case of fungal orbital cellulitis due to Aspergillus in a patient with no history of trauma. A 48-year-old man presented to the emergency room of our hospital with a 2-week history of periorbital swelling, conjunctival hyperemia, and chemosis of his right eye. The visual acuity of his right eye was 6/20, and the intraocular pressure was 44 mmHg. The main clinical findings were proptosis of the right ocular globe with conjunctival hyperemia and a palpable infratemporal orbital mass. Laboratory testing failed to detect the presence of a pathogenic infection, and the lesions on computed tomography images resembled those of a malignant tumor of the orbit. The diagnosis was finally confirmed by postoperative pathological examination, and the patient responded favorably to debridement combined with antifungal therapy. Histopathological examination may help to reveal the nature of this disease. Surgical removal of inflammatory lesions can serve as an important diagnostic and treatment method for fungal orbital cellulitis.

Abstract Polyoxymethylene methacrylate (PMMA) is widely used in ophthalmic biomaterials. Misuse of PMMA in extreme environments is likely to damage the ocular surface and intraocular structures. The surface characterization and tribological behavior of PMMA processed using an excimer laser were investigated in this study by contrasting different lubrication conditions and friction cycles. The results show that the roughness of the material surface increases with laser processing, which changes its physical structure. Under lubrication, the laser-treated PMMA exhibits better hydrophilicity, especially during the use of eye drops. No obvious relationship exists between the laser-processing time and friction behavior. However, the laser treatment may contribute to the formation of friction and wear mechanisms of PMMA materials. Laser-treated PMMA in saline solution exhibits better abrasive resistance by showing a lower wear rate than that in eye drops, although it has a higher friction coefficient. In this study, the different friction stages in laser-treated PMMA were clarified under two lubrication conditions. The wear rates of the laser-treated PMMA were found to decrease with the number of cycles, and the friction coefficient has a similar variation tendency. The wear behavior of the laser-treated PMMA is dominated by the main abrasive wear and secondary transferred film formation. This study provides a theoretical basis for the development and application of ophthalmic biomaterials in complex environments by examining the material surface interface behavior and wear mechanism after laser processing using PMMA as the research matrix.

Abstract Background Erdheim–Chester disease (ECD) is a rare histiocytic disorder characterized by multisystem xanthogranulomatous infiltration by lipid-laden histiocytes. We report two cases of ECD involving the orbit and describe their clinicopathologic factors, treatments, and prognosis. One was a rare case of ECD complicated with primary thrombocytosis. Case presentation This study describes two patients with bilateral orbital ECD. Both presented with proptosis and visual loss; imaging findings showed bilateral intraorbital masses. Both had different degrees of systemic symptoms (pleural effusion, pericardial effusion, ascites, and heart failure) before the ocular symptoms and did not find the cause before ophthalmic tumor resection and pathological biopsy. The diagnosis of ECD was confirmed after pathological biopsy and detection of BRAF V600E mutation. Patient 2 also with primary thrombocytosis and had a CALR mutation as well as the BRAF V600E mutation. Both patients were recommended to receive targeted therapy. Patient 1 refused targeted therapy for financial reasons and was discharged after local radiotherapy only. The patient had no light perception in either eye and no improvement in systemic symptoms. Patient 2 began targeted treatment after diagnosis and reached the discharge criteria 2 weeks later. He is in good condition at present, but unfortunately, his eyesight has not improved because of the irreversible damage to his visual function. Conclusion ECD is easily misdiagnosed and missed because of its rarity and diverse clinical manifestations. Orbital involvement is common in ECD, and surgery is the most frequently employed approach. Despite the surgical resection is not curative, its significance lies in biopsy to establish diagnosis and/or surgical debulking to relieve mass effect, minimizing further impairment of visual function. Targeted therapy is the most effective treatment for patients with a positive BRAF mutation gene. Evaluation of a concomitant myeloid neoplasm is also critical before initiating targeted therapies for refractory ECD.

Abstract Background Ocular trauma is complex and varied, and some occult intraocular foreign bodies (IOFBs) can lead to uncommon symptoms and signs. We report a case of rhegmatogenous retinal detachment (no obvious wound, no pain, no intraocular infection or other symptoms) caused by an occult intraocular aluminium foreign body, which could have been easily missed. Case presentation A 42-year-old male presented to the outpatient department of our hospital complaining of fluttering black dots and decreased vision in his left eye that began 3 months earlier. He was diagnosed with "floaters" at a community hospital. He denied a history of ocular trauma or previous surgery. The cornea and lens of the left eye were clear. A small patch of pigmentation was noted in the temporal sclera. Fundoscopy revealed macula-off retinal detachment. After mydriasis, elliptical holes were seen in the peripheral retina at 2:30, and a suspicious hyperreflective strip was found under the anterior lip of the retina by Goldmann three-mirror contact lens examination; the strip was confirmed to be an IOFB by orbital CT. The IOFB was removed through pars plana vitrectomy without any complications. Conclusion Unlike iron and copper IOFBs, aluminium IOFBs are more inert and more likely to be missed. For people with special occupations (construction workers, mechanics, etc.), when abnormal pigmentation of the sclera is found, the possibility of foreign bodies in the eye should be considered. In the process of disease diagnosis and treatment, it is necessary to ask for a detailed history, including occupation history and practice, and perform careful physical and targeted examinations. Such comprehensive analysis regarding the above information will minimize the chance of missed diagnosis.Awareness of occult IOFB in high risk occupations and prompt referral to a retinal surgeon is of outmost importance.

Neuroendocrine neoplasms (NENs) originate from neuroendocrine cells, and mainly occur in the gastrointestinal tract and lungs, rarely occurring in the orbit. Here, the clinicopathologic factors, treatments and prognosis of three cases of orbital NENs are described. The mean age of the three patients (two females and one male) was 59 years. Two cases exhibited ocular symptoms, including unilateral proptosis and eyelid mass, while the third case presented systemic symptoms exhibited as Cushing’s syndrome. The tumours were surgically resected in all three patients. Immunohistochemistry assays revealed positive expression for pan cytokeratin and epithelial membrane antigen in all cases. Additionally, neural cell adhesion molecule 1 (also known as CD56) and synaptophysin were positive in two cases. The pathological diagnosis for case 1 and 2 was ‘neuroendocrine carcinoma’ and both patients died three months after diagnosis. Case 3 was diagnosed with a neuroendocrine tumour and the symptoms of Cushing’s syndrome gradually improved following surgery. In addition, no recurrence was observed during the four-year follow-up period. These cases demonstrate that orbital neuroendocrine tumours show different clinical manifestations due to the different types. Pathology may clarify the diagnosis, classification and grading, and provide a reference value for treatment and prognosis.

Lacrimal gland mucoepidermoid carcinoma is very rare. It has a high risk of recurrence and metastasis, however, it rarely metastasizes to the contralateral eye in clinical practice. Here, we present a case of a 52-year-old man with lacrimal gland mucoepidermoid carcinoma who developed multiple recurrences and metastases of another eye and other sites throughout the body after receiving surgical intervention and regular radiotherapy, which will be of ophthalmic interest and unique. Clinical features, imaging findings, histopathology, treatments, and outcomes of this very rare case are provided. A literature review of previously published cases of this disease is performed, with an emphasis on the latest diagnosis and treatment. The prognosis of tumor recurrence and metastasis is poorer, surgery with a negative margin in conjunction with adjuvant therapies is crucial for preventing local recurrence and distant metastasis and enhancing the survival rate.

This study aims to observe the accelerated aging effect of 60Co gamma (γ) irradiation on poly (methyl methacrylate) (PMMA) under extreme conditions and determine the influence of different media states on aging. PMMA samples were prepared at room temperature under varying media conditions, including air and deionized water immersion. Then, the samples were irradiated with different doses (50, 250, 500, and 1000 KGy) of 60Co γ-rays. The compositional changes of the PMMA samples exposed to the rays at different periods were determined via Fourier transform infrared spectroscopy. The light transmission of the samples was characterized through ultraviolet-visible spectrophotometry, and the surface wettability of the samples was assessed via water contact angle measurements. Surface and microscopic changes in material morphology were analyzed using optical microscopy, ImageJ software, and scanning electron microscopy. Relative molecular mass and glass transition temperature were analyzed via gel permeation chromatography and differential scanning calorimetry. Thus, a comprehensive analysis of the effect of 60Co γ irradiation on the aging properties of PMMA was performed.

Abstract Background Microspherophakia (MSP, OMIM 251,750) is a rare inherited autosomal recessive eye disorder characterized by small spherically shaped lens. Several studies have indicated that the transforming growth factor-beta (TGF-beta) binding proteins(LTBP2) gene mutation is the predominant cause of MSP. In our study, novel compound heterozygous mutations in the LTBP2 gene associated with MSP were reported, which was different from previous reported homozygous mutations. Case presentation The proband was an 18‐year‐old male in Western China with bilateral MSP, accompanied by ectopia lentis, secondary glaucoma and blindness in both eyes. In our hospital, he received bilateral lens resection and trabeculectomy combined with peripheral iridotomy. Using next-generation sequencing (NGS)-based gene panel tests, we identified pathogenic mutations in the peripheral blood DNA sample from the proband: c.3614_3618dupCTGGC (exon24, NM_000428) and c.2819G > A (exon18, NM_000428). The presence of the novel compound heterozygous mutations in the LTBP2 gene was linked with the development of MSP. Sanger sequencing confirmed the existence of one of the two variants in each parent respectively. Conclusion Our results demonstrated a rare case of MSP phenotype associated with novel compound heterozygous mutations in the LTBP2 gene using NGS technology.

The Kouma Fault, located at the northern foot of the Mangshan Mountain in Luoyang City, Henan Province, China, is an active fault newly discovered in the field seismic geological survey. The Kouma Fault is a normal fault that is approximately 30 km in length, near the east-west strike, and the north dip. The study on the nature of the Quaternary activity of the Kouma Fault is of great significance to the potential seismic source zone division, urban and rural land planning, site selection for major projects, the assessment and prevention of earthquake disaster risk. Through a series of seismic geological surveys, 12 fault outcrops were discovered, which were all distributed on the slopes of the loess gullies. The Kouma Fault cuts loess, clay, sand, and gravel. The fault planes and scratch can be seen clearly. The filling in the fault zone is dominated by clay, loess, and pebbles, among others. When the width of the fault zone is smaller (10–30 cm), most clay in the zone is laminated in occurrence. The laminated surface is almost parallel to the fault plane and the long axis direction of pebbles in the fault zone is almost parallel to the fault plane. When the width of the fault zone is greater (for instance, 1.6 m), the clay and loess in the fault zone are massive. The composite drilling geological section and trench reveal two paleoseismic events of the Kouma Fault, the paleoseismic event I occurred at the fault in the Middle Pleistocene; the paleoseismic event II occurred at the fault in the later period of the Late Pleistocene, and the vertical offset of the upper Pleistocene bottom boundary is 13.57 m. Based on the OSL age data in the fault G1 outcrop of the fault and TC1 and TC2 trenches, the latest activity age of the Kouma Fault may be defined within the range of (38.84 ± 4.69) to (40.90 ± 4.45) kaB.P. The latest active age of the Kouma fault is the late of Late Pleistocene. The average vertical slip rate of the fault during the Late Pleistocene has been 0.11 mm/a.

Abstract Background Although myxofibrosarcoma (MFS) is the most common mesenchymal tumor, occurrence in the orbit is extremely rare. A characteristic clinical feature of MFS is its propensity for local recurrence (LR). Still, none of published literature has described the entire clinical course of multiple recurrences of MFS in the orbit. Here we present an unusual case in which a patient with multiple recurrences of MFS in the orbit followed-up for 5 years. We describe its clinical-pathological correlation, treatment, and prognosis. Case presentation A 70-year-old woman sought treatment for a year history of right upper eyelid swelling in May 2014. Since then, she underwent three surgical procedures in the right orbit in the same region (in 2014, 2016, and 2017). The pathology analysis of the three surgical tissue samples was consistent with myxofibrosarcoma, characterized by spindle-shaped cells and variably myxoid stroma. In the 2 years follow-up after the third surgery, there was no evidence of tumor recurrence. Conclusion Myxofibrosarcoma of the orbit is extremely rare. Since few reports are available in the literature, the diagnosis and management of the orbit myxofibrosarcoma is still a challenge to ophthalmologists. Histopathology is highly valuable in the diagnosis. As a clinical characteristic, the lesions have a high risk of local recurrence; therefore, aggressive resection and careful postoperative follow-up are paramount.

Abstract Background Alveolar soft part sarcoma (ASPS) is a clinically and morphologically distinct malignant soft tissue tumour. It occurs mostly in the lower extremities in adults. The purpose of our study was to describe the related clinicopathologic factors, treatment and prognosis of recurrent orbital ASPS in children. Case presentation Three children aged from 1 to 12 years presented with unilateral proptosis, restricted ocular motility and impaired visual acuity of the affected eye. Periodic acid Schiff (PAS) -positive diastase-resistant crystalline granules were found in all cases. Immunostaining of TFE-3, INL1 and Ki67 was positive in the tumour cells of two patients. The time until local recurrence of primary tumor in patient 2 and patient 3, who only underwent tumour resection, was shorter than that of patient 1, who underwent tumour excision and postoperative radiotherapy. The recurrent masses were successfully treated with complete tumour excision followed by adjuvant radiotherapy. Patient 1 presented metastasis at 11 years after radiotherapy. Conclusions Orbital ASPS in children is easily misdiagnosed due to its rare occurrence and atypical clinical findings. Early diagnosis with multidisciplinary, complete surgical resection combined with adjuvant radiotherapy is essential for achieving long-term disease-free survival in orbital ASPS patients.

Orbitocranial penetrating injuries (OPIs) caused by wooden foreign bodies (WFBs) are very rare and life threatening. Their diagnosis and treatment could be challenging for an ophthalmologist, requiring us to remain alert for possible intracranial extension. We present a case of a 52-year-old man with a residual wooden foreign body in the left frontal lobe. He had a notable history of trauma from a fall on a tree stump and surgical removal of a wooden foreign body from his left orbit 6 years ago. He was referred to us due to recurrent discharge from the eyelid wound. Wooden foreign body residue was successfully removed with a carefully planned craniotomy without complications. This case describes the clinical manifestation, radiographic features, and treatment of this rare trauma, with an emphasis on imaging diagnosis and multi-disciplinary management.

Abstract Background Exome sequencing (ES) has been successfully applied in clinical detection of single nucleotide variants (SNVs) and small indels. However, identification of copy number variants (CNVs) using ES data remains challenging. The purpose of this study is to understand the contribution of CNVs and copy neutral runs of homozygosity (ROH) in molecular diagnosis of patients referred for ES. Methods In a cohort of 11,020 consecutive ES patients, an Illumina SNP array analysis interrogating mostly coding SNPs was performed as a quality control (QC) measurement and for CNV/ROH detection. Among these patients, clinical chromosomal microarray analysis (CMA) was performed at Baylor Genetics (BG) on 3229 patients, either before, concurrently, or after ES. We retrospectively analyzed the findings from CMA and the QC array. Results The QC array can detect ~ 70% of pathogenic/likely pathogenic CNVs (PCNVs) detectable by CMA. Out of the 11,020 ES cases, the QC array identified PCNVs in 327 patients and uniparental disomy (UPD) disorder-related ROH in 10 patients. The overall PCNV/UPD detection rate was 5.9% in the 3229 ES patients who also had CMA at BG; PCNV/UPD detection rate was higher in concurrent ES and CMA than in ES with prior CMA (7.2% vs 4.6%). The PCNVs/UPD contributed to the molecular diagnoses in 17.4% (189/1089) of molecularly diagnosed ES cases with CMA and were estimated to contribute in 10.6% of all molecularly diagnosed ES cases. Dual diagnoses with both PCNVs and SNVs were detected in 38 patients. PCNVs affecting single recessive disorder genes in a compound heterozygous state with SNVs were detected in 4 patients, and homozygous deletions (mostly exonic deletions) were detected in 17 patients. A higher PCNV detection rate was observed for patients with syndromic phenotypes and/or cardiovascular abnormalities. Conclusions Our clinical genomics study demonstrates that detection of PCNV/UPD through the QC array or CMA increases ES diagnostic rate, provides more precise molecular diagnosis for dominant as well as recessive traits, and enables more complete genetic diagnoses in patients with dual or multiple molecular diagnoses. Concurrent ES and CMA using an array with exonic coverage for disease genes enables most effective detection of both CNVs and SNVs and therefore is recommended especially in time-sensitive clinical situations.

Abstract Background Exome sequencing is now being incorporated into clinical care for pediatric and adult populations, but its integration into prenatal diagnosis has been more limited. One reason for this is the paucity of information about the clinical utility of exome sequencing in the prenatal setting. Methods We retrospectively reviewed indications, results, time to results (turnaround time, TAT), and impact of exome results for 146 consecutive “fetal exomes” performed in a clinical diagnostic laboratory between March 2012 and November 2017. We define a fetal exome as one performed on a sample obtained from a fetus or a product of conception with at least one structural anomaly detected by prenatal imaging or autopsy. Statistical comparisons were performed using Fisher’s exact test. Results Prenatal exome yielded an overall molecular diagnostic rate of 32% (n = 46/146). Of the 46 molecular diagnoses, 50% were autosomal dominant disorders (n = 23/46), 41% were autosomal recessive disorders (n = 19/46), and 9% were X-linked disorders (n = 4/46). The molecular diagnostic rate was highest for fetuses with anomalies affecting multiple organ systems and for fetuses with craniofacial anomalies. Out of 146 cases, a prenatal trio exome option designed for ongoing pregnancies was performed on 62 fetal specimens, resulting in a diagnostic yield of 35% with an average TAT of 14 days for initial reporting (excluding tissue culture time). The molecular diagnoses led to refined recurrence risk estimates, altered medical management, and informed reproductive planning for families. Conclusion Exome sequencing is a useful diagnostic tool when fetal structural anomalies suggest a genetic etiology, but other standard prenatal genetic tests did not provide a diagnosis.

Background: There are limited data on what is the minimum change that can be detected in cancer patients undergoing treatment with cardiotoxic drugs and are referred for monitoring left ventricular (LV) function. Objective: To assess the variability in the measurement of LV volumes and ejection fraction (EF) in contrast echocardiography and to determine the minimum detectable difference (MDD) between two EF measurements that can be deemed significant. Methods: A total of 150 patients were divided into three groups according to EF (EF 60%). Each group consisted of 50 randomly selected cancer patients who underwent contrast echocardiography between July 2010 and May 2014. Repeated measurements of LV volumes and EF were performed offline by a sonographer and a cardiologist. Inter-observer variability was assessed by analysis of variance. Measurement error was estimated by standard error of measurement and MDD. Results: The 95% confidence interval with a single measurement of EF was 2 percentage points in the groups of patients with EF 60%, and 2.5 percentage points for patients with EF 53–60%. The MDD for EF, end-diastolic volume and end-systolic volume that could be recognized with 95% confidence interval were 4 percentage points, 7 mL and 4 mL, respectively. Conclusion: Contrast echocardiography is a reliable tool for serial measurements of EF to monitor cardiotoxicity due to chemotherapy. In a high-volume echocardiography laboratory with experienced staff, the MDD for EF of 4 percentage points on a good-quality recording demonstrates the high reproducibility of the Simpson’s method using contrast echocardiography.

Neonatal cholestasis is a result of elevated bile acid levels, and is associated with mutations in genes regulating bile acid homeostasis. Here the authors identify mutations in the bile acid sensing farnesoid X receptor in four individuals with neonatal cholestasis from two unrelated families.

The nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPAR𝛾) is an important transcription factor regulating adipocyte differentiation, lipid and glucose homeostasis, and insulin sensitivity. Numerous genetic mutations of PPAR𝛾 have been identified and these mutations positively or negatively regulate insulin sensitivity. Among these, a relatively common polymorphism of PPAR𝛾, Pro12Ala of PPAR𝛾2, the isoform expressed only in adipose tissue has been shown to be associated with lower body mass index, enhanced insulin sensitivity, and resistance to the risk of type 2 diabetes in human subjects carrying this mutation. Subsequent studies in different ethnic populations, however, have revealed conflicting results, suggesting a complex interaction between the PPAR𝛾2 Pro12Ala polymorphism and environmental factors such as the ratio of dietary unsaturated fatty acids to saturated fatty acids and/or between the PPAR𝛾2 Pro12Ala polymorphism and genetic factors such as polymorphic mutations in other genes. In addition, this polymorphic mutation in PPAR𝛾2 is associated with other aspects of human diseases, including cancers, polycystic ovary syndrome, Alzheimer disease and aging. This review will highlight findings from recent studies.