| Autor: |
Lepe-Balsalobre E; Molecular Diagnosis and Rare Diseases Laboratory, Department of Clinical Biochemistry, Hospital Universitario Virgen del Rocío, Seville, Spain.; Fundación JL Castaño, Sociedad Española de Medicina de Laboratorio, Barcelona, Spain., Santotoribio JD; Molecular Diagnosis and Rare Diseases Laboratory, Department of Clinical Biochemistry, Hospital Universitario Virgen del Rocío, Seville, Spain., Nuñez-Vazquez R; Unidad de Hemofilia, Department of Hematology, Hospital Universitario Virgen del Rocío, Seville, Spain., García-Morillo S; Unidad de Colagenosis y Enfermedades Minoritarias, Unidad Experimental de Riesgo Cardiovascular, Department of Internal Medicine, Hospital Universitario Virgen del Rocío, Seville, Spain., Jiménez-Arriscado P; Molecular Diagnosis and Rare Diseases Laboratory, Department of Clinical Biochemistry, Hospital Universitario Virgen del Rocío, Seville, Spain., Hernández-Arévalo P; Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI), Hospital Universitario Virgen del Rocío, Seville, Spain., Delarosa-Rodríguez R; Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI), Hospital Universitario Virgen del Rocío, Seville, Spain., Guerrero JM; Molecular Diagnosis and Rare Diseases Laboratory, Department of Clinical Biochemistry, Hospital Universitario Virgen del Rocío, Seville, Spain., Macher HC; Molecular Diagnosis and Rare Diseases Laboratory, Department of Clinical Biochemistry, Hospital Universitario Virgen del Rocío, Seville, Spain. |
| Abstrakt: |
Objectives Gaucher disease (GD) is the most common inherited lysosomal storage disease, caused by mutations in acid β-glucosidase (GBA) gene. This study aimed to identify mutations in Andalusia patients with GD and their genotype-phenotype correlation. Methods Descriptive observational study. University Hospital Virgen del Rocio patients diagnosed from GD from 1999 to 2019 were included. Demographic and clinical data, β-glucocerebrosidase activity, variants pathogenic in GBA gene and biomarkers for monitoring treatment were collected from digital medical record. Results Twenty-six patients with aged between 1 day and 52 years were studied. A total of six mutations described as pathogenic and one mutation not described above [c.937T>C (p.Tyr313His)] were identified in the GBA gene, four patients were homozygotes and 22 compound heterozygotes. Twenty-four patients were diagnosed in non-neuropathic form (type 1) and two cases presented neurological involvement (type 2 or 3). The most common variant was c.1226A>G (p.Asn409Ser), which was detected in 24 patients, followed by c.1448T>C (p.Leu483Pro) variant, identified in 13 patients. The c.1448T>C (p.Leu483Pro) mutation has been presented in the most severe phenotypes with neurological involvement associated with type 2 and 3 GD, while c.1226A>G (p.Asn409Ser) mutation has not been associated with neurological alterations. Splenomegaly and bone disease were the most frequent clinical manifestations, and thrombocytopenia was the most common hematological disorder. Conclusions The c.1226A>G (p.Asn409Ser) and c.1448T>C (p.Leu483Pro) mutations were the most common. The c.937T>C (p.Tyr313His) was identified as a novel mutation. The c.1448T>C (p.Leu483Pro) mutation was associated with neurological alterations and c.1226A>G (p.Asn409Ser) mutation has not been associated it. |
