Genetic and clinical features of patients with Gaucher disease in Hungary

Erdős, Melinda; Hodaňová, Kateřina; Taskó, Szilvia; Palicz, Anita; Stolnaja, Larisa; Dvořáková, Lenka; Hřebı́ček, Martin; Maródi, László

doi:10.1016/j.bcmd.2007.02.005

Cited by 20 publications

(12 citation statements)

References 29 publications

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“…The 12 patients homozygous for L444P who succumbed to early severe visceral GD could be first classified as having GD1. 36 , 37 …”

Section: Discussionmentioning

confidence: 99%

Gaucher disease in Syrian children: common mutations identification and clinical futures

Alasmar

2015

Annals of Saudi Medicine

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BACKGROUND AND OBJECTIVESGaucher disease (GD) is caused by the deficiency of glucosidase beta acid (GBA). Three clinical forms of GD are available. Some mutations in the GBA gene have a high frequency in specific populations. The aim of this study was to analyze the characteristics of phenotypes and genotypes of GD in Syrian pediatric patients and assess whether a genotype-phenotype relationship could be helpful in treatment decision-making.DESIGN AND SETTINGSA cross-sectional clinical genetic study of 19 Syrian children admitted to Children’s Hospital, Damascus University.PATIENTS AND METHODSNineteen Syrian children with GD were enrolled in the study; DNA was extracted from peripheral blood leukocytes. The GBA gene was amplified by polymerase chain reaction, and the 9 most common mutations were studied using a Gaucher Disease Strip Assay (ViennaLab Diagnostics GmbH, Vienna, Austria).RESULTSThe majority of children had an early age of onset. A total of 17 patients presented severe hematological and skeletal complications. Neurological involvement was encountered in 2 patients. Twelve patients (63, 2%) were homozygous for the L444P mutation, 1 patient (5.3%) was homozygous for the N370S mutation, and 1 patient (5.3%) was heterozygous for the N370S mutation. Five patients (26.3%) had unknown mutations.CONCLUSIONL444P/L444P was the most common genotype in the studied patients. GD3 with severe visceral presentation in childhood was the dominant phenotype; N370S was found in the heterozygote state in 1 case and in the homozygote state in 1 case. This phenotype and genotype pattern is encountered in the Middle East. There was no genotype-phenotype correlation.

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“…The 12 patients homozygous for L444P who succumbed to early severe visceral GD could be first classified as having GD1. 36 , 37 …”

Section: Discussionmentioning

confidence: 99%

Gaucher disease in Syrian children: common mutations identification and clinical futures

Alasmar

2015

Annals of Saudi Medicine

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“…In the HGMD mutation database only 3 exonic mutations leading to GD are reported as disrupting the proper mRNA splicing process. Two of them are missense mutations, which alter the natural splice donor sites [ 10 , 28 ], and one is a silent mutation introducing a cryptic donor splice site [ 8 ]. Therefore, we report the first silent mutation altering the proper splicing process through loss of an ESE sequence, hence resulting in GD.…”

Section: Discussionmentioning

confidence: 99%

Progressive myoclonus epilepsy in Gaucher Disease due to a new Gly–Gly mutation causing loss of an Exonic Splicing Enhancer

et al. 2018

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BackgroundPatients with Gaucher Disease (GD) exhibit three phenotypes, including type 1 (non-neuronopathic), type 2 (acute neuronopathic), and type 3 (subacute neuronopathic).AimIdentifying which GBA changes represent benign polymorphisms and which may result in disease-causing mutations is essential for diagnosis and genotype/phenotype correlations but is often challenging.ResultsHere, we describe a patient with type 3 GD, presenting with drug-resistant epilepsy, who bears a set of GBA polymorphic variants including the novel c.363A > G (Gly82Gly) synonymous mutation. In silico predictions, mRNA and functional studies revealed that the new Gly82Gly mutation causes skipping of GBA exon 4, leading to a severe reduction of the wild type GBA mRNA. This is the first report of a synonymous change causing GD through loss of an exonic splicing enhancer sequence.The synonymous mutation is in trans with the Asn188Ser missense mutation, thus making the Asn188Ser responsible for the patient’s phenotype and strengthening the association of Asn188Ser with the particular neurological phenotype of type 3 GD.ConclusionWe strengthen the association of Asn188Ser with the type 3 GD phenotype and progressive myoclonus epilepsy. Our data confirm that in silico predictions and mRNA analysis are mandatory in discriminating pathological mutations from the background of harmless polymorphisms, especially synonymous changes.

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“…78.50 RecNciI Czech and Slovak [6] N370S 76 L444P RecNciI Ashkenazi Jews [7] N370S, 93 c.84-85insG IVS2 + 1G-->A L444P Hungarian [8] N370S…”

Section: Frequency Of Mutations (%)mentioning

confidence: 99%

Gaucher disease: New developments in treatment and etiology

Harmancı

Bayraktar²

2008

WJG

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Gaucher disease (GD) is an autosomal recessive disease which if undiagnosed or diagnosed late results in devastating complications. Because of the heterozygous nature of GD, there is a wide spectrum of clinical presentation. Clinicians should be aware of this rare but potentially treatable disease in patients who present with unexplained organomegaly, anemia, massive splenomegaly, ascites and even cirrhosis of unknown origin. The treatment options for adult type GD include enzyme replacement treatment (ERT) and substrate reduction treatment (SRT) depending on the status of the patient. Future treatment options are gene therapy and "smart molecules" which provide specific cure and additional treatment options. In this review, we present the key issues about GD and new developments that gastroenterologists should be aware of.

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Genetic and clinical features of patients with Gaucher disease in Hungary

Cited by 20 publications

References 29 publications

Gaucher disease in Syrian children: common mutations identification and clinical futures

Gaucher disease in Syrian children: common mutations identification and clinical futures

Progressive myoclonus epilepsy in Gaucher Disease due to a new Gly–Gly mutation causing loss of an Exonic Splicing Enhancer

Gaucher disease: New developments in treatment and etiology

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