Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Our ability to identify different variants in GBA1, the gene mutated in the lysosomal storage disorder Gaucher disease (GD), has greatly improved. We describe a multigenerational family with type 1 GD initially evaluated over three decades ago. Re-evaluating both the genotype and phenotype, we determined that one family member with genotype N370S/T369M (p.N409S/p.T408M), was likely erroneously diagnosed with GD. This case substantiates that GBA1 variant T369M, while mildly reducing glucocerebrosidase activity, does not result in GD. The observation has clinical relevance as cases with this genotype will increasingly be ascertained through screening programs in newborns and in movement disorder clinics.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/ajmg.a.63345 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Case Report: A case of surgical and enzyme replacement therapy for type I Gaucher disease complicating femoral shaft pathological fracture.
Front Surg
August 2025
Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Gaucher disease (GD) is an inherited lysosomal storage disorder caused by glucocerebrosidase (GCase) deficiency. A 35-year-old male patient was admitted to our hospital due to left thigh pain and restricted mobility for 10 h. Following comprehensive evaluations, the patient was diagnosed with GD complicated by a pathological fracture of the left femur.
View Article and Find Full Text PDFNavigating the Emotional and Practical Challenges of Newborn Screening for Late-Onset Pompe Disease: Insights From Parental Perspectives.
Pediatr Neurol
August 2025
Division of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina. Electronic address:
Pompe disease (PD), an autosomal recessive lysosomal disorder, results in glycogen accumulation in muscle cells, leading to progressive muscle weakness and respiratory insufficiency. Newborn screening (NBS) has improved outcomes for infantile-onset PD by enabling early diagnosis and intervention with enzyme replacement therapy. NBS also identifies late-onset PD (LOPD) cases, wherein children have a wide clinical spectrum and may remain asymptomatic for years, placing families in uncertainty as "patients-in-waiting.
View Article and Find Full Text PDFAddition of Lyso-Gb1 to enzyme activity to first-tier test for Gaucher in DBS improves diagnostic accuracy and reduces patient recall rate.
Clin Chim Acta
August 2025
Laboratorio Chamoles, Uriarte 2383, C1425FNH Ciudad Autónoma de Buenos Aires, Argentina; Sanofi Argentina, Cuyo 3532, B1640GJC Martínez, Provincia de Buenos Aires, Argentina.
Introduction: The gold standard for diagnosing Gaucher disease (GD) is the detection of reduced beta-glucosidase (bGlu) activity in peripheral blood samples, in association with variant analysis of the GBA1 gene. Dried blood spot (DBS) specimens are accepted worldwide for first-tier testing of GD. Glucosylsphingosine (Lyso-Gb1) is considered an ideal disease biomarker.
View Article and Find Full Text PDFGaucher disease type 1 is a lysosomal storage disorder caused by mutations that reduce glucocerebrosidase activity, leading to glycolipid buildup, particularly in macrophages. To develop a curative approach, we established a high-efficiency genome editing platform for human and murine hematopoietic stem-progenitor cells using CRISPR/Cas9, recombinant adeno-associated virus serotype 6. To enhance homology-directed DNA repair while minimizing genotoxicity, we incorporated a new 53BP1 inhibitor, a ubiquitin variant that promotes DNA end resection and significantly increases editing efficiency.
View Article and Find Full Text PDFThe Double Toxic MPTP+CBE Presymptomatic Parkinson-Like Phenotype in Mice.
Biochemistry (Mosc)
August 2025
Institute of Molecular Genetics, Kurchatov Institute National Research Centre, Moscow, 123182, Russia.
The deficiency of glucocerebrosidase (GCase) encoded by the gene, leads to the autosomal recessive Gaucher disease and highly increased risk of developing Parkinson's disease (PD). In order to study the effect of GCase dysfunction on neurodegeneration, we evaluated the GCase activity, lysosphingolipid content, extent of dopaminergic neuron degeneration in the substantia nigra (SN), and levels of dopamine (DA) and total and oligomeric α-synuclein (α-Syn) in the brain of mice with the presymptomatic stage of parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in combination with a single injection of the GCase selective inhibitor conduritol-β-epoxide (CBE) (100 mg/kg body weight). A single injection of CBE led to a ~50% decrease in the GCase activity, significant increase in the lysosphingolipid content, and striatal accumulation of oligomeric α-Syn in the mouse brain.
View Article and Find Full Text PDF