scholarly journals A novel mutation deep within intron 7 of the GBA gene causes Gaucher disease

2020 ◽  
Vol 8 (3) ◽  
Author(s):  
Anna Malekkou ◽  
Ioanna Sevastou ◽  
Gavriella Mavrikiou ◽  
Theodoros Georgiou ◽  
Lluisa Vilageliu ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Novel Mutation ◽  
Gba Gene

scholarly journals Phenotype diversity in type 1 Gaucher disease: discovering the genetic basis of Gaucher disease/hematologic malignancy phenotype by individual genome analysis

Blood ◽  
2012 ◽  
Vol 119 (20) ◽  
pp. 4731-4740 ◽  
Author(s):  
Sarah M. Lo ◽  
Murim Choi ◽  
Jun Liu ◽  
Dhanpat Jain ◽  
Rolf G. Boot ◽  
...  
Keyword(s):  
Genome Analysis ◽  
Gaucher Disease ◽  
Genetic Basis ◽  
Massively Parallel Sequencing ◽  
Novel Mutation ◽  
Genetic Modifier ◽  
Exome Capture ◽  
Individual Genome ◽  
Cancer Phenotype ◽  
Gba Gene

Abstract Gaucher disease (GD), an inherited macrophage glycosphingolipidosis, manifests with an extraordinary variety of phenotypes that show imperfect correlation with mutations in the GBA gene. In addition to the classic manifestations, patients suffer from increased susceptibility to hematologic and nonhematologic malignancies. The mechanism(s) underlying malignancy in GD is not known, but is postulated to be secondary to macrophage dysfunction and immune dysregulation arising from lysosomal accumulation of glucocerebroside. However, there is weak correlation between GD/cancer phenotype and the systemic burden of glucocerebroside-laden macrophages. Therefore, we hypothesized that genetic modifier(s) may underlie the GD/cancer phenotype. In the present study, the genetic basis of GD/T-cell acute lymphoblastic lymphoma in 2 affected siblings was deciphered through genomic analysis. GBA gene sequencing revealed homozygosity for a novel mutation, D137N. Whole-exome capture and massively parallel sequencing combined with homozygosity mapping identified a homozygous novel mutation in the MSH6 gene that leads to constitutional mismatch repair deficiency syndrome and increased cancer risk. Enzyme studies demonstrated that the D137N mutation in GBA is a pathogenic mutation, and immunohistochemistry confirmed the absence of the MSH6 protein. Therefore, precise phenotype annotation followed by individual genome analysis has the potential to identify genetic modifiers of GD, facilitate personalized management, and provide novel insights into disease pathophysiology.

scholarly journals Accurate Molecular Diagnosis of Gaucher Disease Using Clinical Exome Sequencing as a First-Tier Test

2021 ◽  
Vol 22 (11) ◽  
pp. 5538
Author(s):  
Stefania Zampieri ◽  
Silvia Cattarossi ◽  
Eleonora Pavan ◽  
Antonio Barbato ◽  
Agata Fiumara ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Molecular Diagnosis ◽  
Gaucher Disease ◽  
Novel Mutation ◽  
Large Deletion ◽  
Clinical Exome Sequencing ◽  
Number Variation ◽  
Long Range Pcr ◽  
Set Up ◽  
Beta Glucosidase

Gaucher disease (GD) is an autosomal recessive lysosomal disorder due to beta-glucosidase gene (GBA) mutations. The molecular diagnosis of GD is complicated by the presence of recombinant alleles originating from a highly homologous pseudogene. Clinical exome sequencing (CES) is a rapid genetic approach for identifying disease-causing mutations. However, copy number variation and recombination events are poorly detected, and further investigations are required to avoid mis-genotyping. The aim of this work was to set-up an integrated strategy for GD patients genotyping using CES as a first-line test. Eight patients diagnosed with GD were analyzed by CES. Five patients were fully genotyped, while three were revealed to be homozygous for mutations that were not confirmed in the parents. Therefore, MLPA (multiplex ligation-dependent probe amplification) and specific long-range PCR were performed, and two recombinant alleles, one of them novel, and one large deletion were identified. Furthermore, an MLPA assay performed in one family resulted in the identification of an additional novel mutation (p.M124V) in a relative, in trans with the known p.N409S mutation. In conclusion, even though CES has become extensively used in clinical practice, our study emphasizes the importance of a comprehensive molecular strategy to provide proper GBA genotyping and genetic counseling.

Identification and Characterization of a Novel Mutation c.1090G>T (G325W) and Nine Common Mutant Alleles Leading to Gaucher Disease in Spanish Patients

2001 ◽  
Vol 27 (2) ◽  
pp. 489-495 ◽  
Author(s):  
M.A. Torralba ◽  
J.I. Pérez-Calvo ◽  
G.M. Pastores ◽  
A. Cenarro ◽  
P. Giraldo ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Novel Mutation ◽  
Identification And Characterization

Molecular studies on parents after autopsy identify recombinant GBA gene in a case of Gaucher disease with ichthyosis phenotype

2015 ◽  
Vol 167 (11) ◽  
pp. 2858-2860 ◽  
Author(s):  
Shagun Aggarwal ◽  
S. Jamal Mohamed Nurul Jain ◽  
Aneek D. Bhowmik ◽  
Ashwani Tandon ◽  
Ashwin Dalal
Keyword(s):  
Gaucher Disease ◽  
Molecular Studies ◽  
Gba Gene

Determining the frequency of common mutations in the GBA gene in patients with Gaucher disease in Ukraine

2007 ◽  
Vol 41 (4) ◽  
pp. 230-236
Author(s):  
N. G. Gorovenko ◽  
N. V. Ol’khovich ◽  
A. M. Nedoboy ◽  
N. O. Pichkur
Keyword(s):  
Gaucher Disease ◽  
Gba Gene

scholarly journals Splenomegaly, Cardiomegaly, and Osteoporosis in a Child with Gaucher Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-4
Author(s):  
J. J. Sheth ◽  
C. M. Ankleshwaria ◽  
M. A. Mistri ◽  
N. Nanavaty ◽  
S. J. Mehta
Keyword(s):  
Gaucher Disease ◽  
Molecular Study ◽  
Carrier Status ◽  
Pulmonary Congestion ◽  
Severe Osteoporosis ◽  
Massive Splenomegaly ◽  
Heterozygous Condition ◽  
Chorionic Villi ◽  
Gba Gene ◽  
Reduced Activity

A 15-month-old girl, born to the consanguineous parents, was referred with the sign of massive splenomegaly associated with thrombocytopenia and anemia. Plasma Chitotriosidase estimation was carried out as a screening test and was found to be normal with reduced activity ofβ-glucosidase in leucocytes suggestive of Gaucher disease. At the age of 4 years, severe osteoporosis and cardiomegaly with pulmonary congestion were observed in the child. Molecular analysis for GBA gene has revealed homozygous status for L444P (c.1448C) in the proband, whereas parents and two elder sisters were found to be heterozygote. Prenatal study during the fourth pregnancy was carried out from cultured chorionic villi forβ-glucosidase, which was in the carrier range. Further confirmation of the carrier status was carried out from amniotic fluid DNA and was found to be heterozygous for L444P (c.1448C) in theGBAgene. This case demonstrates that children with the sign of splenomegaly with anemia and thrombocytopenia need to be screened for Gaucher disease, and molecular study can further help to confirm the heterozygous status, where prenatal study by enzyme investigation demonstrate heterozygous condition.

scholarly journals Identification of GBA Gene Mutations in 19 Pakistani Unrelated Patients of Gaucher Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4952-4952 ◽  
Author(s):  
Arshi Naz ◽  
Qurat Abedin ◽  
Shariq Ahmed ◽  
Saima Siddiqui ◽  
Tahir Shamsi
Keyword(s):  
Bone Marrow ◽  
Genetic Analysis ◽  
Gene Mutation ◽  
Gaucher Disease ◽  
Conflicts Of Interest ◽  
Demographic Data ◽  
White Blood Cells ◽  
Bone Marrow Morphology ◽  
Number Of Patients ◽  
Gba Gene

Abstract Introduction: Gaucher disease (GD) is one of the lysosomal storage diseases that is rare and inherited autosomal recessively. There is insufficiency of glucocerebrosidase enzyme that leads to the build up of un-degraded substrates in white blood cells causing anemia, hepatosplenomegaly and skeletal disease. This enzyme deficiency is linked with the defect of its gene (GBA) that codes for this enzyme. Initial diagnosis is made by the estimation of glucocerebrosidase level in blood and confirmed by genetic analysis of GBA gene. To identify the mutations of GBA gene in Pakistani patients with GD from different regions of Pakistan. Sampling & methodology: The sample and demographic data was collected in National Institute of Blood Disease and Bone marrow Transplantation after approval of IRB and written informed consent of patients. We collected total 19 blood samples, out of which 5 had Gaucher's disease, 10 samples were parents of the index cases and 4 were control. The methodology consisted of DNA extraction and quantification from peripheral blood. Genetic analysis of coding regions of GBA gene was done via gene amplification, gel electrophoresis and sequencing. Result: Mutation was found in two out of five families that makes the prevalence of GBA gene mutation 40%. These were diagnosed on reduced enzyme levels and found to have L444P (c.1448T>C) mutation in homozygous form in 10th exon of GBA gene. The parents of that patient carried the same mutation in one allele. Rest of the patients who were diagnosed on bone marrow morphology showed no mutation in GBA gene. Conclusion: Our results illustrate that GBA gene mutation was found in those patients who were diagnosed by the estimation of β-glucosidase enzyme levels rather than on bone marrow morphology. In our population, the mutation L444P was found, which is the most frequent gene mutation found in the world. Since this study is conducted in a small number of patients therefore it is recommended that large cohorts of patients should be evaluated in future for genetic mutations among Gaucher's patients in Pakistan Key words: Gaucher disease, storage disorder, GBA gene Disclosures No relevant conflicts of interest to declare.

A novel mutation (V191G) in a German-British type 1 Gaucher disease patient

1998 ◽  
Vol 11 (5) ◽  
pp. 411-412 ◽  
Author(s):  
Francis Y. M. Choy ◽  
M. Lisa Humphries ◽  
Yoav Ben-Yoseph
Keyword(s):  
Gaucher Disease ◽  
Novel Mutation ◽  
Disease Patient ◽  
Type 1 Gaucher Disease

Novel mutation, L371V, causing multigenerational Gaucher disease in a Lebanese family

2004 ◽  
Vol 125A (3) ◽  
pp. 257-260 ◽  
Author(s):  
A. Shamseddine ◽  
A. Taher ◽  
S. Fakhani ◽  
M. Zhang ◽  
C. Ronald Scott ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Novel Mutation
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