Laboratory diagnosis and follow-up of Romanian Gaucher disease patients
Background: Gaucher disease (GD) is caused by a recessively inherited deficiency of glucocerebrosidase which is encoded by the GBA gene in which nearly 450 mutations have been described. However, only a few genotype- phenotype correlations have been clearly established. The aim of this study was to...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Sciendo
2017-07-01
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| Series: | Romanian Journal of Laboratory Medicine |
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| Online Access: | https://doi.org/10.1515/rrlm-2017-0018 |
| _version_ | 1819117003997184000 |
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| author | Drugan Cristina Drugan Tudor Caillaud Catherine Grigorescu-Sido Paula Nistor Tiberiu Crăciun Alexandra M. |
| author_facet | Drugan Cristina Drugan Tudor Caillaud Catherine Grigorescu-Sido Paula Nistor Tiberiu Crăciun Alexandra M. |
| author_sort | Drugan Cristina |
| collection | DOAJ |
| description | Background: Gaucher disease (GD) is caused by a recessively inherited deficiency of glucocerebrosidase which is encoded by the GBA gene in which nearly 450 mutations have been described. However, only a few genotype- phenotype correlations have been clearly established. The aim of this study was to investigate molecular features of GD in Romanian patients and to evaluate their impact on treatment response. Material and methods: 69 patients, diagnosed between 1997 and 2014 at our national referral laboratory, were included in this study. Frequent point mutations (N370S, L444P, 84GG, R463C) were detected by amplification and restriction enzyme digestion. Recombinant alleles (recTL, recNciI, recA456P) were screened by DNA sequencing. Plasma chitotriosidase served as a biomarker of disease severity throughout the follow-up period. Results: 66 patients had the non-neuronopathic (type 1) form of GD and 3 had the chronic neuronopathic (type 3) phenotype. We identified 79% of the mutant alleles, among which the most frequent mutations were N370S (54%) and L444P (18%). We found a statistically significant (p<0.001) and moderate to good correlation between the total therapeutic dose and the residual chitotriosidase activity (R = 0.621). After two years of treatment, we noticed statistically significant variations in chitotriosidase activity corresponding to the most frequent genotypes (N370S/ unknown allele, N370S/L444P, N370S/N370S and N370S/R463Q). Conclusions: Allele distribution displayed specific features in Romanian GD patients, such as the high prevalence of the N370S allele. Chitotriosidase activity measurement allowed the investigation of genotype influence on treatment outcome. |
| first_indexed | 2024-12-22T05:26:05Z |
| format | Article |
| id | doaj.art-5254ed254de4456087f259571cecb4c2 |
| institution | Directory Open Access Journal |
| issn | 2284-5623 |
| language | English |
| last_indexed | 2024-12-22T05:26:05Z |
| publishDate | 2017-07-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Romanian Journal of Laboratory Medicine |
| spelling | doaj.art-5254ed254de4456087f259571cecb4c22022-12-21T18:37:34ZengSciendoRomanian Journal of Laboratory Medicine2284-56232017-07-0125327528510.1515/rrlm-2017-0018rrlm-2017-0018Laboratory diagnosis and follow-up of Romanian Gaucher disease patientsDrugan Cristina0Drugan Tudor1Caillaud Catherine2Grigorescu-Sido Paula3Nistor Tiberiu4Crăciun Alexandra M.5Department of Medical Biochemistry, „Iuliu Haţieganu“ University of Medicine and Pharmacy, Cluj-Napoca, RomaniaDepartment of Medical Informatics and Biostatistics, „Iuliu Haţieganu“ University of Medicine and Pharmacy, Cluj-Napoca, RomaniaLaboratoire de Biochimie, Métabolomique et Protéomique, Hôpital Necker‐Enfants Malades, University Paris Descartes, FranceDepartment of Paediatrics I, „Iuliu Haţieganu“ University of Medicine and Pharmacy, Cluj-Napoca, RomaniaDepartment of Medical Biochemistry, „Iuliu Haţieganu“ University of Medicine and Pharmacy, Cluj-Napoca, RomaniaDepartment of Medical Biochemistry, „Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, RomaniaBackground: Gaucher disease (GD) is caused by a recessively inherited deficiency of glucocerebrosidase which is encoded by the GBA gene in which nearly 450 mutations have been described. However, only a few genotype- phenotype correlations have been clearly established. The aim of this study was to investigate molecular features of GD in Romanian patients and to evaluate their impact on treatment response. Material and methods: 69 patients, diagnosed between 1997 and 2014 at our national referral laboratory, were included in this study. Frequent point mutations (N370S, L444P, 84GG, R463C) were detected by amplification and restriction enzyme digestion. Recombinant alleles (recTL, recNciI, recA456P) were screened by DNA sequencing. Plasma chitotriosidase served as a biomarker of disease severity throughout the follow-up period. Results: 66 patients had the non-neuronopathic (type 1) form of GD and 3 had the chronic neuronopathic (type 3) phenotype. We identified 79% of the mutant alleles, among which the most frequent mutations were N370S (54%) and L444P (18%). We found a statistically significant (p<0.001) and moderate to good correlation between the total therapeutic dose and the residual chitotriosidase activity (R = 0.621). After two years of treatment, we noticed statistically significant variations in chitotriosidase activity corresponding to the most frequent genotypes (N370S/ unknown allele, N370S/L444P, N370S/N370S and N370S/R463Q). Conclusions: Allele distribution displayed specific features in Romanian GD patients, such as the high prevalence of the N370S allele. Chitotriosidase activity measurement allowed the investigation of genotype influence on treatment outcome.https://doi.org/10.1515/rrlm-2017-0018gaucher diseasegenotype-phenotype correlationschitotriosidaseenzyme replacement therapyromanian population |
| spellingShingle | Drugan Cristina Drugan Tudor Caillaud Catherine Grigorescu-Sido Paula Nistor Tiberiu Crăciun Alexandra M. Laboratory diagnosis and follow-up of Romanian Gaucher disease patients Romanian Journal of Laboratory Medicine gaucher disease genotype-phenotype correlations chitotriosidase enzyme replacement therapy romanian population |
| title | Laboratory diagnosis and follow-up of Romanian Gaucher disease patients |
| title_full | Laboratory diagnosis and follow-up of Romanian Gaucher disease patients |
| title_fullStr | Laboratory diagnosis and follow-up of Romanian Gaucher disease patients |
| title_full_unstemmed | Laboratory diagnosis and follow-up of Romanian Gaucher disease patients |
| title_short | Laboratory diagnosis and follow-up of Romanian Gaucher disease patients |
| title_sort | laboratory diagnosis and follow up of romanian gaucher disease patients |
| topic | gaucher disease genotype-phenotype correlations chitotriosidase enzyme replacement therapy romanian population |
| url | https://doi.org/10.1515/rrlm-2017-0018 |
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