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Abstract Background Aminoacyl-tRNA synthetases (ARSs) are indispensable enzymes for protein biosynthesis in cells. The phenylalanyl-tRNA synthetase (FARS1) located in cytoplasm which consists of two FARS alpha subunits (FARSA) and two FARS beta subunits (FARSB). Autosomal recessive inheritance of pathogenic variants of FARSA or FARSB can result in defective FARS1 which are characterized by interstitial lung disease, liver disease, brain abnormalities, facial dysmorphism and growth restriction. Methods Exome sequencing was used to detect the candidate variants. The in silico prediction and expressional level analysis were performed to evaluate the pathogenicity of the variations. Additionally, we presented the patient’s detailed clinical information and compared the clinical feature with other previously reported patients with FARSA-deficiency. Results We identified compound heterozygous rare missense variants (c.1172 T > C/ p.Leu391Pro and c.1211G > A/ p.Arg404His) in FARSA gene in a Chinese male patient. The protein structure prediction and the analysis of levels of FARSA and FARSB subunits indicated both variants pathogenic. Clinical feature review indicated inflammatory symptoms in young infants may be an additional key feature. Thyroid dysfunction should be considered as a phenotype with variable penetrance. Conclusions Our results expanded the current phenotypic and genetic spectrum of FARSA-deficiency.

Abstract Background Intellectual disability (ID) is a con neurodevelopmental disorder in children. The genetic etiology of ID is complex, but more subtypes are defined due to the broad application of next‐generation sequencing. Methods Whole‐exome sequencing (WES) and Sanger sequencing was applied in a family with ID. Results We report a Chinese 7.5‐year‐old boy, born to non‐consanguineous parents. He showed severe intellectual disability, seizures and autistic features. Two previously unreported variants in MBOAT7, c.669C>G (p.(Tyr223*)) and c.1095C>G (p.(Ser365Arg)) were identified by trio‐WES. His mother is a heterozygous carrier of the c.1095C>G variant. The c.669C>G variant is a de novo variant which was undetected in his parents. By construction of the full‐length cDNA of the patient's MBOAT7, we verified that these two variants were trans‐compound heterozygous variants, which support the genetic etiology of this patient. Conclusion This patient is the first Chinese case of intellectual developmental disorder (IDD), autosomal recessive 57 (OMIM:617188) with two unreported MBOAT7 variants.

Objective To explore the clinical effect of endoscopic strip craniectomy with orthotic skull helmet for sagittal synostosis. Methods A total of 20 children with sagittal synostosis admitted to Shanghai Children's Hospital from June 2019 to June 2022 were included. All of them underwent endoscopic strip craniectomy and customized orthotic skull helmet assisted treatment after the surgery. Cephalic index (CI) and point of maximum width (PMW) were calculated by measuring transverse diameter of skull, anterior and posterior diameter of skull, and distance between eyebrow and transverse diameter of skull. Results All 20 sagittal synostosis children successfully completed the surgery, the success rate of the surgery was 100%, and no indwelling drainage tube was placed in the surgical area. There were no postoperative complications such as bone flap displacement, cerebrospinal fluid leakage, secondary infection, nerve function defect caused by skull osteotomy and secondary injury caused by bone fragments ionization. At 6 months after sugery and last follow⁃up, 19 children showed a favorable prognosis in terms of cranial shape, while one 2⁃month⁃old female child had an unfavorable head shape prognosis (CI was 72% at 6 months after sugery, and 74% at the last follow⁃up). There were statistically significant differences between CI (F = 230.542, P = 0.000) and PMW (F = 112.166, P = 0.000) before and after surgery. Among them, CI (t = ⁃ 14.231, P = 0.000; t = ⁃ 21.041, P = 0.000) and PMW (t = ⁃ 8.068, P = 0.000; t = ⁃ 16.109, P = 0.000) at 6 month after surgery and last follow⁃up were higher than those before surgery. CI (t = ⁃ 6.810, P = 0.000) and PMW (t = ⁃ 8.040, P = 0.000) at last follow⁃up were higher than those at 6 month after surgery. Conclusions Endoscopic strip craniectomy with orthotic skull helmet can improve the cranial shape of children with sagittal synostosis and is considered safe and effective.

Objective To analyze clinical efficacy and influencing factors of selective dorsal rhizotomy (SDR) for treatment of spastic cerebral palsy (SCP) in children. Methods Total 131 children with SCP who underwent SDR at Shanghai Children's Hospital between September 2015 and June 2019 were included in the study. The Gross Motor Function Classification System (GMFCS) and Gross Motor Function Measure-66 Items (GMFM-66) were used to evaluate the gross motor function before surgery and at the last follow-up. The modified Ashworth Scale was used to assess the degree of spasticity in the target muscle groups of the lower limbs. Univariate and multivariate Logistic regression analyses were performed to identify the influencing factors of the improvement in GMFM -66 score. Results Compared to preoperative values, there was a significant decrease in muscle tonus in the target muscle groups of the lower limbs after surgery, including bilateral adductors muscles (Z = -8.164, P = 0.000; Z = -8.304, P = 0.000), bilateral hamstrings muscles (Z = -7.424, P = 0.000; Z = -7.123, P = 0.000), bilateral gastrocnemius muscles (Z = -9.328, P = 0.000; Z = -9.605, P = 0.000), and bilateral tibialis anterior muscles (Z = -9.349, P = 0.000; Z = -9.543, P = 0.000). The overall improvement rate of GMFCS classification after surgery was 34.35% (45/131), and there were no cases of GMFCS classification worsening. There were statistically significant differences in GMFM -66 scores before and after surgery among different GMFCS levels (F = 215.030, P = 0.000). The improvement in GMFM -66 score was greater in GMFCS level Ⅰ (t = 4.379, P = 0.000), Ⅱ (t = 3.686, P = 0.000) and Ⅲ (t = 3.198, P = 0.002) compared to level Ⅳ , and levelⅠ had better score than level Ⅲ (t = 2.170, P = 0.032). Logistic regression analysis showed that surgery performed at the age of 3-6 years (OR = 4.917, 95%CI: 1.554-15.557; P = 0.007) and preoperative GMFCS level Ⅰ - Ⅲ (OR = 10.294, 95%CI: 3.522- 30.092; P = 0.000) were favorable factors for a ΔGMFM -66 score improvement of ≥ 6.55 score. Conclusions SDR effectively reduces muscle tonus in the target muscle groups of the lower limbs and improves gross motor function in children with SCP. The treatment outcome is particularly favorable for children with increased muscle tonus in both lower limbs who can cooperate with rehabilitation training (GMFCS level Ⅰ-Ⅲ). SDR can also be considered for children with severe cerebral palsy (GMFCS level Ⅳ-Ⅴ) to facilitate daily care.

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare disease characterized by appearance of premature aging, including the skin, bones, heart, and blood vessels caused by LMNA mutation. In this study, the patient presented with congenital micrognathia and progressively aggravated upper airway obstruction as the initial symptom, which required bilateral mandibular distraction osteogenesis (MDO) surgery intervention. This was not commonly described in the literature, and the primary clinical diagnosis of Pierre Robin sequence (PRS) was made. However, other clinical features included sclerotic skin, dry skin, growth failure, lipoatrophy, joint stiffness, prominent scalp veins, small ear lobes, hair loss, and craniofacial disproportion gradually emerged, the diagnosis of HGPS was preferred when the patient was 5 months old. The genetic testing result with a novel and de novo LMNA mutation (c.1968 + 3_1968+6delGAGT) further confirmed the diagnosis and expanded the clinical and mutational spectrum of HGPS. During the 12-month follow-up period after surgery, the patient no longer suffered dyspnea. Complications of other organs and systems have not happened at the moment. In addition, the pathogenesis, the role of LMNA gene mutation, the progress in clinical treatment, and breakthrough studies about genetic treatment in animals of HGPS are described in the literature review.

TPC2 is an important organellar Na+/Ca2+ release channel which regulates function of lysosomes and lysosome-related organelles. Here, Wang et al. demonstrate that a gain-of-function mutation (R210C) in TPC2 leads to hypopigmentaion, enlarged endolysosomes, enhanced lysosomal Ca2+ release and hyper-acidification.

ObjectiveSarcopenia has been recognized as the third category of disabling complications in patients with type 2 diabetes mellitus(T2DM), in addition to micro- and macrovascular complications. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are innovative glucose-lowering treatments that have been shown to reduce body weight and enhance cardiovascular and renal outcomes. However, there is vigilance that SGLT2 inhibitors should be taken cautiously because they target skeletal muscle and may raise the risk of sarcopenia. Herein, we conducted a meta-analysis of randomized controlled trials to evaluate the effects of SGLT2 inhibitors on sarcopenia in patients with T2DM.MethodRelevant studies were obtained from PubMed, Embase, Medicine, Cochrane, and Web of Science databases to determine eligible studies until February 2023, without any language restrictions. A random effects model was utilized irrespective of heterogeneity, and the I2 statistic was used to evaluate study heterogeneity. The differences in results were measured using the weighted average difference (WMD) of the continuous data, along with a 95% confidence interval (CI).ResultsA total of 25 randomized controlled trials with 2,286 participants were included. SGLT2 inhibitors significantly reduced weight-related changes and fat-related changes, including body weight(BW) (WMD= -2.74, 95% CI: -3.26 to -2.23, P

Although the complete nucleotide sequence of strawberry vein banding virus (SVBV) has been determined and bioinformatic analysis has revealed that the SVBV genome could encode seven proteins, the precise function of each protein is unclear. This study provided evidence that the P1 protein of SVBV (SVBV-P1) possesses the following features. Bioinformatic and subcellular localization analyses showed that SVBV-P1 is localized in the cytoplasm and cell walls of epidermal cells in Nicotiana benthamiana, and it forms inclusion bodies associated with microtubules and the endoplasmic reticulum. Dilution experiments demonstrated that SVBV-P1 could move from the original agro-infiltrated cells to adjacent cells in N. benthamiana leaves. Further trans-complementation experiments demonstrated that SVBV-P1 could facilitate the intercellular movement of a movement-deficient potato virus X mutant in N. benthamiana leaves. Finally, yeast two-hybrid and bimolecular fluorescence complementation assays revealed that SVBV-P1 could interact with the SVBV coat protein, which is a major component of Caulimovirus virions. Results of the electrophoretic mobility shift assay indicated that SVBV-P1 lacks DNA-binding capability. In summary, the results suggest that SVBV-P1 is probably a movement protein of SVBV, providing new insights into the function of movement proteins of the Caulimovirus genus.