Table1_Identification of a De Novo Heterozygous Missense ACTB Variant in Baraitser–Winter Cerebrofrontofacial Syndrome.DOCX

Baraitser–Winter cerebrofrontofacial syndrome (BWCFF, OMIM: 243310) is a rare autosomal-dominant developmental disorder associated with variants in the genes ACTB or ACTG1. It is characterized by brain malformations, a distinctive facial appearance, ocular coloboma, and intellectual disability. However, the phenotypes of BWCFF are heterogenous, and its molecular pathogenesis has not been fully elucidated. In the present study, we conducted detailed clinical examinations on a Chinese patient with BWCFF and found novel ocular manifestations including pseudoduplication of the optic disc and nystagmus. Targeted gene panel sequencing and Sanger sequencing identified a de novo heterozygous missense c.478A > G (p.Thr160Ala) variant in ACTB. The mRNA and protein expression of ACTB was assessed by quantitative reverse transcription PCR and Western blots. Furthermore, the functional effects of the pathogenic variant were analyzed by protein structure analysis, which indicated that the variant may affect the active site for ATP hydrolysis by the actin ATPase, resulting in abnormal filamentous actin organization in peripheral blood mononuclear cells. This discovery extends the ACTB variant spectrum, which will improve genetic counseling and diagnosis, and may contribute to understanding the pathogenic mechanisms of actin-related diseases.</p

Comparison of clinic-pathologic characteristics of 178 patients according to postoperative NLR change.

<p>AFP, a-fetoprotein; ALB, serum albumin; ALT, alanine aminotransferase; ALP, alkaline phosphatase; AST, aspartate aminotransferase; γ-GGT, gamma glutamyl transpeptidase; HBeAg, hepatitis B e-antigen; NLR, neutrophil- lymphocyte ratio; PLT, platelets; PT, prothrombin time; RFA, radiofrequency ablation; T-bil, total bilirubin; WBC, white blood cell.</p

Graphs show the overall survival curves for different subgroup patients with postoperative NLR decreased and increased after RFA.

<p>Graphs show the overall survival curves for different subgroup patients with postoperative NLR decreased and increased after RFA.</p

Graphs show the overall survival curves for patients with postoperative NLR decreased and increased after RFA.

<p>The difference between groups were statistically significant (log-rank test, <i>P</i><0.001).</p

Cox proportional hazards model of baseline prognosticators for new recurrence in 178 patients with small HCC undergoing RFA.

<p>AFP, a-fetoprotein; CI, confidence interval; HBeAg, hepatitis B e-antigen; HR, hazard ratio; NLR, neutrophil-lymphocyte ratio; RFA, radiofrequency ablation.</p

Table_1_Abnormal lens thickening in a child with Weill–Marchesani syndrome 4: A 3-year follow-up case report.DOCX

BackgroundWeill–Marchesani syndrome 4 (WMS4) is caused by ADAMTS17 gene variant and clinical abnormalities including lenticular myopia, ectopia lentis, glaucoma, microspherophakia, brachydactyly, and short stature. Due to free of heart defects and joint stiffness compared with other WMS forms, WMS4 has an insidious onset and is often misdiagnosed as high myopia. We combined multiple imaging biometry and whole-exome sequencing to diagnose a case of WMS4 with a 3-year follow-up.Case presentationAn 8-year-old boy presented to our ophthalmology department with progressive myopia for 1 year. He had high myopia in both eyes with normal funds, intraocular pressure, and axial length. Ocular examination revealed thicker lenses (right 4.38 mm, left 4.31 mm) with a smaller equatorial diameter (right 7.33 mm and left 7.17 mm) compared to normal children of the same age. Finger length measurement indicates brachydactyly. Whole-exome sequencing identified compound heterozygous missense variants c.2984G > A (p.Arg995Gln) and c.2254A > G (p.Ile752Val) in the ADAMTS17 gene. During the 3 years of follow-up, the thickness of lenses increased significantly (right 4.49 mm, left 4.48 mm), but the equatorial diameter of the lenses had no significant change (right 7.32 mm, left 7.21 mm). As the equivalent lens power increased, the patient’s myopia spherical refractive error rose accordingly. Although the anterior chamber angle remained open during follow-up, the intraocular pressure increased to right 20.4 mmHg and left 19.6 mmHg, Iridodonesis and short stature were present.ConclusionThis case report highlights the abnormal thickening of the lens in WMS4 compared to the physiological thinning process during childhood. Comprehensive clinical examinations and genetic testing may improve diagnosis, which allows early therapeutic interventions for complications and better visual outcomes for the patient.</p

Graphs show the recurrence free survival curves for different subgroup patients with postoperative NLR decreased and increased after RFA.

<p>Graphs show the recurrence free survival curves for different subgroup patients with postoperative NLR decreased and increased after RFA.</p

Video_1_Abnormal lens thickening in a child with Weill–Marchesani syndrome 4: A 3-year follow-up case report.MP4

BackgroundWeill–Marchesani syndrome 4 (WMS4) is caused by ADAMTS17 gene variant and clinical abnormalities including lenticular myopia, ectopia lentis, glaucoma, microspherophakia, brachydactyly, and short stature. Due to free of heart defects and joint stiffness compared with other WMS forms, WMS4 has an insidious onset and is often misdiagnosed as high myopia. We combined multiple imaging biometry and whole-exome sequencing to diagnose a case of WMS4 with a 3-year follow-up.Case presentationAn 8-year-old boy presented to our ophthalmology department with progressive myopia for 1 year. He had high myopia in both eyes with normal funds, intraocular pressure, and axial length. Ocular examination revealed thicker lenses (right 4.38 mm, left 4.31 mm) with a smaller equatorial diameter (right 7.33 mm and left 7.17 mm) compared to normal children of the same age. Finger length measurement indicates brachydactyly. Whole-exome sequencing identified compound heterozygous missense variants c.2984G > A (p.Arg995Gln) and c.2254A > G (p.Ile752Val) in the ADAMTS17 gene. During the 3 years of follow-up, the thickness of lenses increased significantly (right 4.49 mm, left 4.48 mm), but the equatorial diameter of the lenses had no significant change (right 7.32 mm, left 7.21 mm). As the equivalent lens power increased, the patient’s myopia spherical refractive error rose accordingly. Although the anterior chamber angle remained open during follow-up, the intraocular pressure increased to right 20.4 mmHg and left 19.6 mmHg, Iridodonesis and short stature were present.ConclusionThis case report highlights the abnormal thickening of the lens in WMS4 compared to the physiological thinning process during childhood. Comprehensive clinical examinations and genetic testing may improve diagnosis, which allows early therapeutic interventions for complications and better visual outcomes for the patient.</p

Graphs show the recurrence free survival curves for patients with preoperative NLR≥1.9 and NLR<1.9.

<p>The difference between groups were not statistically significant (log-rank test, <i>P</i> = 0.859).</p

Graphs show the recurrence free survival curves for patients with postoperative NLR decreased and increased after RFA.

<p>The difference between groups were statistically significant (log-rank test, <i>P</i><0.001).</p