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Licensed Unlicensed Requires Authentication Published by De Gruyter June 25, 2020

Genotype/phenotype relationship in Gaucher disease patients. Novel mutation in glucocerebrosidase gene

  • Esperanza Lepe-Balsalobre , José D. Santotoribio ORCID logo EMAIL logo , Ramiro Nuñez-Vazquez , Salvador García-Morillo , Pilar Jiménez-Arriscado , Paula Hernández-Arévalo , Rocío Delarosa-Rodríguez , Juan M. Guerrero and Hada C. Macher



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.


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.


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.


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.

Corresponding author: José D. Santotoribio, Molecular Diagnosis and Rare Diseases Laboratory, Department of Clinical Biochemistry, Hospital Universitario Virgen del Rocío, Seville, Spain, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: This study adhered to the ethical recommendations of the Declaration of Helsinki (Fortaleza, 2013) [11], and was approved by the Ethics and Research Committee of the Virgen Macarena and Virgen del Rocio University Hospitals (Code: 0826-N-15).


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Received: 2020-03-12
Accepted: 2020-05-21
Published Online: 2020-06-25

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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