New pathogenic variants of ALMS1 gene in two Chinese families with Alström Syndrome.

PURPOSE: Alström Syndrome (AS) is an autosomal recessive hereditary disease with the characteristics of multiorgan dysfunction. Due to the heterogeneity of clinical manifestations of AS, genetic testing is crucial for the diagnosis of AS. Herein, we used whole-exome sequencing (WES) to determine the genetic causes and characterize the clinical features of three affected patients in two Chinese families with Alström Syndrome. MATERIALS AND METHODS: Three affected patients (initially diagnosed as achromatopsia). and five asymptomatic members were recruited for both genetic and clinical tests. The complete ophthalmic examinations and systemic examinations were performed on all participants. Whole exome sequencing (WES) was performed for mutation detection. The silico analysis was also applied to predict the pathogenesis of identified pathogenic variants. RESULTS: In family 1, the proband showed low vision, hyperopia, photophobia, nystagmus, and total color blindness. DNA analysis revealed that she carried a compound heterozygote with two novel pathogenic variants in the ALMS1 gene NM_015120.4:c.10379del (NP_055935.4:p.(Asp2252Tyr)) and NM_015120.4:c.11641_11642del (NP_055935.4:p.(Val3881ThrfsTer11)). Further systemic examinations showed short stature, acanthosis nigricans, and sensorineural hearing loss. In family 2, two affected siblings presented the low vision, hyperopia, photophobia, nystagmus, and total color blindness. DNA analysis revealed that they carried a same compound heterozygote with two novel pathogenic variants in the ALMS1 gene NM_015120.4:c.10379del (NP_055935.4:p.(Asn3460IlefsTer49)), NM_015120.4:c.10819C > T (NP_055935.4:p.(Arg3607Trp)). Further systemic examinations showed obesity and mild abnormalities of lipid metabolism. According to the genetic testing results and further systemic analysis, the three affected patients were finally diagnosed as Alström Syndrome (AS). CONCLUSIONS: We found two new compound heterozygous pathogenic variants of the ALMS1 gene and determined the diagnosis as Alström Syndrome in three patients of two Chinese families. Our study extends the genotypic and phenotypic spectrums for ALMS1 -AS and emphasizes the importance of gene testing in assisting the clinical diagnosis for cases with phenotypic diversities, which would help the AS patients with early diagnosis and treatment to reduce future systemic damage.

Dye-sensitized solar cells with reduced graphene oxide as the counter electrode prepared by a green photothermal reduction process.

Highly conductive reduced graphene oxide (rGO) with good electrocatalytic ability for reducing triiodide ions (I3(-)) is a promising catalyst for the counter electrode (CE) of dye-sensitized solar cells (DSSCs). However, hazardous chemical reducing agents or energy-consuming thermal treatments are required for preparing rGO from graphene oxide (GO). Therefore, it is necessary to find other effective and green reduction processes for the preparation of rGO and to fabricate rGO-based DSSCs. In this study, GO was prepared using a modified Hummers method from graphite powder, and further reduced to rGO through a photothermal reduction process (to give P-rGO). P-rGO shows better electrocatalytic ability due mainly to its high standard heterogeneous rate constant for I3(-) reduction and in part to its considerable electrochemical surface area. The corresponding DSSC shows a higher cell efficiency (η) of 7.62% than that of the cell with a GO-based CE (η=0.03%). When the low-temperature photothermal reduction process is applied to all-flexible plastic DSSCs, the DSSC with a P-rGO CE shows an η of 4.16%.

Urinary stone analysis and clinical characteristics of 496 patients in Taiwan.

Evaluate urinary stone components' epidemiological features in urolithiasis individuals and explore potential correlations between stone components and patients' clinical characteristics. A retrospective analysis of urinary stone compositions in 496 patients from a northern Taiwan medical center (February 2006 to October 2021) was conducted. We investigated associations between sex, age, body mass index (BMI), hypertension, diabetes mellitus (DM), hyperlipidemia (HLP), gout, coronary artery disease (CAD), cerebral vascular accident (CVA), chronic kidney disease (CKD), habits, urine pH, and three main stone groups: calcium oxalate (CaOx), calcium phosphate (CaP), and uric acid (UA). Males accounted for 66.5% of cases, with a male-to-female ratio of 1.99:1. Males were negatively associated with CaP stones (OR 0.313, p < 0.001) and positively with UA stones (OR 2.456, p = 0.009). Age showed a negative correlation with CaOx stones (OR 0.987, p = 0.040) and a positive correlation with UA stones (OR 1.023, p < 0.001). DM had a protective effect against CaP stones (OR 0.316, p = 0.004). Gout had a positive association with UA stones (OR 2.085, p = 0.035). Smoking was adversely associated with UA stones (OR 0.350, p = 0.018). Higher urine pH was a risk factor for CaP stones (OR 1.641, p = 0.001) and a protective factor against UA stones (OR 0.296, p < 0.001). These results may provide insights into the pathogenesis of urinary stones and the development of preventative strategies for high-risk populations. Further research is required to confirm and expand upon these findings.

Identification of genetic variants in five chinese families with keratoconus: Pathogenicity analysis and characteristics of parental corneal topography.

Purpose: The study aims to identify genetic variants in five Chinese families with Keratoconus (KC) and describe the characteristics of parental corneal topography. Methods: Fifteen participants, including five probands and ten parents from five Chinese families with KC, were recruited for genetic and clinical analyses. Targeted next-generation sequencing using a custom-designed panel for KC was applied on the probands for variant identification. Sanger sequencing and cosegregation analysis of the suspected pathogenic variants were performed on the family members. The pathogenicities of variants were evaluated according to the American College of Medical Genetics and Genomics guidelines (ACMG). Pentacam 3D anterior segment analysis system was applied for keratectasia detection and the Corvis ST for corneal biomechanics measurement. Fifteen parameters were recorded, including nine keratectasia indicators (BAD-D, TP, Kmax, Df, Db, Dp, Dt, Da, ARTH), six corneal biomechanical indicators (CBI, DA ratio, SP-A1, IR, bIOP, TBI). Results: A total of six novel variants, including five missense variants and one frameshift variant, were detected in the HMX1, SLC4A11, TGFBI, PIKFYVE, and ZEB1 genes in five probands, all of which showed co-segregation of genotype and clinical phenotype and were determined to be pathogenic. The genetic model was autosomal dominant (AD) in four families and autosomal recessive (AR) in 1 family. The analysis of keratectasia and corneal biomechanical indicators of the proband's parents (first-generation relatives) in AD families revealed that there were several abnormal indexes in BAD-D, TP, Kmax, Df, Db, Dp, Dt, Da, CBI, DA ratio, SP-A1, IR, bIOP and TBI test indexes, showing clinical characteristics of incipient KC. Conclusion: Our study shows that variants in HMX1, SLC4A11, TGFBI, PIKFYVE, and ZEB1 were associated with KC. Our study extends the gene spectrum associated with KC, provides novel insights into KC phenotypic assessments, and contributes to early diagnosis for these patients.