The Novel Compound Heterozygous Mutations in the AGL Gene in a Chinese Family With Adult Late-Onset Glycogen Storage Disease Type IIIa

Qu, Qianqian; Qian, Qi; Shi, Jiejing; Liu, Haiyan; Zhang, Yan; Chen, Ping; Lv, Haidong

doi:10.3389/fneur.2020.554012

Cited by 2 publications

(1 citation statement)

References 19 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GSD III ( AGL , MIM# 232400), VI ( PYGL , MIM# 232700) and IXα ( PHKA2 , MIM# 306000) belong to hepatic GSD with basic features of hepatomegaly and hypoglycemia ( Beyzaei et al, 2020 ). They share commonalities also in other clinical signs: metabolic abnormalities, short stature, and motor development delay/muscle weakness with aging, that lead to challenging to identify the subtypes of patients with hepatic GSD, especially between VI and IX ( Qu et al, 2020 ; Szymanska et al, 2021 ). However, some subtypes have been found to have specific phenotypic features, for example growth delay is more common in GSD IX patients than in VI patients and hypoglycemia was more pronounced in GSD III than GSD VI and IX ( Kishnani et al, 2019 ; Fernandes et al, 2020 ; Grunert et al, 2021b ).…”

Section: Discussionmentioning

confidence: 99%

Genotypic and phenotypic characteristics of 12 chinese children with glycogen storage diseases

et al. 2022

View full text Add to dashboard Cite

Background: Glycogen storage diseases (GSDs) are known as a group of disorders characterized by genetic errors leading to accumulation of glycogen in various tissues. Since different types of GSD can sometimes be clinically indistinguishable, next generation sequencing is becoming a powerful tool for clinical diagnosis.Methods: 12 patients with suspected GSDs and their parents were enrolled in this study. The clinical and laboratory data of the patients were reviewed. Causative gene variants were identified in the patients using whole exome sequencing (WES) and verified by Sanger sequencing.Results: Genetic testing and analysis showed that 7 patients were diagnosed with GSD II (Pompe disease), 2 patients with GSD III, 1 patient with GSD VI, and 2 patients with GSD IXα. A total number of 18 variants were identified in 12 patients including 11 variants in GAA gene, 3 variants in AGL gene, 2 variants in PYGL gene and 2 variants in PHKA2 gene, of which 9 variants were reported and 9 variants were novel. SIFT, Polyphen-2, Mutation Taster, and REVEL predicted the novel variants (except GAA c.1052_1075 + 47del) to be disease-causing. The 3D structures of wild/mutant type GAA protein were predicted indicating that variants p. Trp621Gly, p. Pro541Leu, p. Ser800Ile and p. Gly293Trp might affect the proteins function via destroying hydrogen bonds or conformational constraints. Neither liver size nor laboratory findings allow for a differentiation among GSD III, GSD VI and GSD IXα.Conclusion: Our study expanded the variation spectrum of genes associated with GSDs. WES, in combination with clinical, biochemical, and pathological hallmarks, could provide accurate results for diagnosing and sub-typing GSD and related diseases in clinical setting.

show abstract

Section: Discussionmentioning

confidence: 99%

Genotypic and phenotypic characteristics of 12 chinese children with glycogen storage diseases

et al. 2022

View full text Add to dashboard Cite

show abstract

Honeycomb-like biomimetic scaffold by functionalized antibacterial hydrogel and biodegradable porous Mg alloy for osteochondral regeneration

Zhang,

Dong,

Zhao

et al. 2024

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Introduction: Osteochondral repair poses a significant challenge due to its unique pathological mechanisms and complex repair processes, particularly in bacterial tissue conditions resulting from open injuries, infections, and surgical contamination. This study introduces a biomimetic honeycomb-like scaffold (Zn-AlgMA@Mg) designed for osteochondral repair. The scaffold consists of a dicalcium phosphate dihydrate (DCPD)-coated porous magnesium scaffold (DCPD Mg) embedded within a dual crosslinked sodium alginate hydrogel (Zn-AlgMA). This combination aims to synergistically exert antibacterial and osteochondral integrated repair properties.Methods: The Zn-AlgMA@Mg scaffold was fabricated by coating porous magnesium scaffolds with DCPD and embedding them within a dual crosslinked sodium alginate hydrogel. The structural and mechanical properties of the DCPD Mg scaffold were characterized using scanning electron microscopy (SEM) and mechanical testing. The microstructural features and hydrophilicity of Zn-AlgMA were assessed. In vitro studies were conducted to evaluate the controlled release of magnesium and zinc ions, as well as the scaffold’s osteogenic, chondrogenic, and antibacterial properties. Proteomic analysis was performed to elucidate the mechanism of osteochondral integrated repair. In vivo efficacy was evaluated using a rabbit full-thickness osteochondral defect model, with micro-CT evaluation, quantitative analysis, and histological staining (hematoxylin-eosin, Safranin-O, and Masson’s trichrome).Results: The DCPD Mg scaffold exhibited a uniform porous structure and superior mechanical properties. The Zn-AlgMA hydrogel displayed consistent microstructural features and enhanced hydrophilicity. The Zn-AlgMA@Mg scaffold provided controlled release of magnesium and zinc ions, promoting cell proliferation and vitality. In vitro studies demonstrated significant osteogenic and chondrogenic properties, as well as antibacterial efficacy. Proteomic analysis revealed the underlying mechanism of osteochondral integrated repair facilitated by the scaffold. Micro-CT evaluation and histological analysis confirmed successful osteochondral integration in the rabbit model.Discussion: The biomimetic honeycomb-like scaffold (Zn-AlgMA@Mg) demonstrated promising results for osteochondral repair, effectively addressing the challenges posed by bacterial tissue conditions. The scaffold’s ability to release magnesium and zinc ions in a controlled manner contributed to its significant osteogenic, chondrogenic, and antibacterial properties. Proteomic analysis provided insights into the scaffold’s mechanism of action, supporting its potential for integrated osteochondral regeneration. The successful in vivo results highlight the scaffold’s efficacy, making it a promising biomaterial for future applications in osteochondral repair.

show abstract

The Novel Compound Heterozygous Mutations in the AGL Gene in a Chinese Family With Adult Late-Onset Glycogen Storage Disease Type IIIa

Cited by 2 publications

References 19 publications

Genotypic and phenotypic characteristics of 12 chinese children with glycogen storage diseases

Genotypic and phenotypic characteristics of 12 chinese children with glycogen storage diseases

Honeycomb-like biomimetic scaffold by functionalized antibacterial hydrogel and biodegradable porous Mg alloy for osteochondral regeneration

Contact Info

Product

Resources

About