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

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

doi:10.1515/cclm-2020-0306

Article

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

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

Published/Copyright: June 25, 2020

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 58 Issue 12

Abstract

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.

Keywords: bone disease; Gaucher disease; GBA gene; β-glucocerebrosidase enzyme; massive sequencing; splenomegaly; thrombocytopenia

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

Research funding: None declared.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
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

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Articles in the same Issue

https://doi.org/10.1515/cclm-2020-0306

Keywords for this article

bone disease; Gaucher disease; GBA gene; β-glucocerebrosidase enzyme; massive sequencing; splenomegaly; thrombocytopenia