Brazilian patients with Gaucher disease: Haplotype analysis

2021 ◽  
Vol 132 (2) ◽  
pp. S97
Author(s):  
Ida V.D. Schwartz ◽  
Amanda Pasqualotto ◽  
Vivian Altmann ◽  
Rafael H. Tresbach ◽  
Fernanda Sperb-Ludwig ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Haplotype Analysis ◽  
Disease Haplotype

scholarly journals The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects

2020 ◽  
Author(s):  
Yoo-Mi Kim ◽  
Jin-Ho Choi ◽  
Gu-Hwan Kim ◽  
Young Bae Sohn ◽  
Jung-Min Ko ◽  
...  
Keyword(s):  
Founder Effect ◽  
Gaucher Disease ◽  
Clinical Characteristics ◽  
Haplotype Analysis ◽  
Study Cohort ◽  
Ashkenazi Jewish ◽  
Founder Effects ◽  
Neuroprotective Effects ◽  
Shared Haplotype

Abstract Background Gaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA. Haplotype analyses previously demonstrated founder effects for particular GBA mutations in Ashkenazi Jewish and French-Canadian populations. This study aimed to investigate the clinical characteristics and mutation spectrum of GBA in Korean GD patients and to identify founder effect of GBA p.G85E in non-neuronopathic GD patients. Results The study cohort included 63 GD patients from 58 unrelated families. Among them, 18 patients from 17 families harboured the p.G85E mutation. Haplotype analysis was performed for 9 probands and their parents for whom DNA samples were available. In 58 unrelated probands, the GBA mutation p.L483P was the most common (30/116 alleles, 26%), followed by p.G85E (16%), p.F252I (13%), and p.R296Q (10%). Of the 18 patients harbouring the p.G85E mutation, their median age at diagnosis was 3.8 (range 1.2–57) years. No patients developed neurological symptoms during follow-up periods of 2.2–20.3 (median 13.9) years. The size of the shared haplotype containing GBA p.G85E was 732 kbp, leading to an estimated age of 3,075 years. Conclusion The GBA p.G85E mutation, which appears to be neuroprotective despite producing distinctive visceromegaly and skeletal symptoms, exhibited a potential founder effect in Korean GD patients.

scholarly journals Clinicopathologic and molecular spectrum of RNASEH1-related mitochondrial disease

2017 ◽  
Vol 3 (3) ◽  
pp. e149 ◽  
Author(s):  
Enrico Bugiardini ◽  
Olivia V. Poole ◽  
Andreea Manole ◽  
Alan M. Pittman ◽  
Alejandro Horga ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Mitochondrial Disease ◽  
Haplotype Analysis ◽  
Progressive External Ophthalmoplegia ◽  
Mtdna Deletions ◽  
Clinical Presentations ◽  
Human Rnase ◽  
Disease Haplotype ◽  
Founder Event ◽  
Pathophysiologic Mechanisms

Objective:Pathologic ribonuclease H1 (RNase H1) causes aberrant mitochondrial DNA (mtDNA) segregation and is associated with multiple mtDNA deletions. We aimed to determine the prevalence of RNase H1 gene (RNASEH1) mutations among patients with mitochondrial disease and establish clinically meaningful genotype-phenotype correlations.Methods:RNASEH1 was analyzed in patients with (1) multiple deletions/depletion of muscle mtDNA and (2) mendelian progressive external ophthalmoplegia (PEO) with neuropathologic evidence of mitochondrial dysfunction, but no detectable multiple deletions/depletion of muscle mtDNA. Clinicopathologic and molecular evaluation of the newly identified and previously reported patients harboring RNASEH1 mutations was subsequently undertaken.Results:Pathogenic c.424G>A p.Val142Ile RNASEH1 mutations were detected in 3 pedigrees among the 74 probands screened. Given that all 3 families had Indian ancestry, RNASEH1 genetic analysis was undertaken in 50 additional Indian probands with variable clinical presentations associated with multiple mtDNA deletions, but no further RNASEH1 mutations were confirmed. RNASEH1-related mitochondrial disease was characterized by PEO (100%), cerebellar ataxia (57%), and dysphagia (50%). The ataxia neuropathy spectrum phenotype was observed in 1 patient. Although the c.424G>A p.Val142Ile mutation underpins all reported RNASEH1-related mitochondrial disease, haplotype analysis suggested an independent origin, rather than a founder event, for the variant in our families.Conclusions:In our cohort, RNASEH1 mutations represent the fourth most common cause of adult mendelian PEO associated with multiple mtDNA deletions, following mutations in POLG, RRM2B, and TWNK. RNASEH1 genetic analysis should also be considered in all patients with POLG-negative ataxia neuropathy spectrum. The pathophysiologic mechanisms by which the c.424G>A p.Val142Ile mutation impairs human RNase H1 warrant further investigation.

scholarly journals The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects

2020 ◽  
Author(s):  
Yoo-Mi Kim ◽  
Jin-Ho Choi ◽  
Gu-Hwan Kim ◽  
Young Bae Sohn ◽  
Jung-Min Ko ◽  
...  
Keyword(s):  
Founder Effect ◽  
Gaucher Disease ◽  
Clinical Characteristics ◽  
Haplotype Analysis ◽  
Study Cohort ◽  
Ashkenazi Jewish ◽  
Founder Effects ◽  
Neuroprotective Effects ◽  
Shared Haplotype

Abstract Background Gaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA. Haplotype analyses previously demonstrated founder effects for particular GBA mutations in Ashkenazi Jewish and French-Canadian populations. This study aimed to investigate the clinical characteristics and mutation spectrum of GBA in Korean GD patients and to identify founder effect of GBA p.G85E in non-neuronopathic GD patients. Results The study cohort included 62 GD patients from 58 unrelated families. Among them, 18 patients from 17 families harbored the p.G85E mutation. Haplotype analysis was performed for 9 probands and their parents for whom DNA samples were available. In 58 unrelated probands, the GBA mutation p.L483P was the most common (30/116 alleles, 26%), followed by p.G85E (16%), p.F252I (13%), and p.R296Q (9%). The median age at diagnosis of the 18 patients harboring the p.G85E mutation was 3.8 (range 1.2–57) years. No patients developed neurological symptoms during follow-up periods of 2.2–20.3 (median 13.9) years. The size of the shared haplotype containing GBA p.G85E was 732 kbp, leading to an estimated age of 3,075 years. ConclusionThe GBA p.G85E mutation, which appears to be neuroprotective despite producing distinctive visceromegaly and skeletal symptoms, exhibited a potential founder effect in Korean GD patients.

scholarly journals Association ofApolipoprotein A1-C3Gene Cluster Polymorphisms with Gallstone Disease

2007 ◽  
Vol 21 (9) ◽  
pp. 569-575 ◽  
Author(s):  
Manjusha Dixit ◽  
Gourdas Choudhuri ◽  
Rajan Saxena ◽  
Balraj Mittal
Keyword(s):  
Haplotype Analysis ◽  
Gallstone Disease ◽  
Apolipoprotein A1 ◽  
Control Analysis ◽  
Apolipoprotein C3 ◽  
Disease Case ◽  
Version 2.0 ◽  
Disease Haplotype ◽  
Case Control Analysis ◽  
Very High

INTRODUCTION: Genetic polymorphisms in apolipoprotein genes may be associated with alteration in lipid profile and susceptibility to gallstone disease.AIM: To determine the association betweenapolipoprotein A1(APOA1) (−75 guanine [G] to adenine [A] and +83/84 M2+/−,MspI) andapolipoprotein C3(APOC3) (SstI) polymorphisms with gallstone disease.METHODS:MspIpolymorphisms of theAPOA1gene andSstIpolymorphisms ofAPOC3were analyzed in DNA samples of 214 gallstone patients and 322 age- and sex-matched healthy controls. All statistical analyses were performed using SPSS version 11.5 (SPSS, USA) and Arlequin version 2.0 (Arlequin, Switzerland).RESULTS: TheAPOA1−75 G/A polymorphism was significantly associated with gallstone disease. Patients with the GG genotype (P=0.015) and G allele carriers (P=0.004) had a significantly higher risk of gallstone disease (1.087-fold and 1.561-fold, respectively), whereas patients with AA genotypes (P=0.011) and A allele carriers (P=0.004) were protected (OR 0.230 and 0.641, respectively) against gallstone disease.APOA1+83 M2+/−andAPOC3 SstIpolymorphisms were not associated with gallstone disease. Case-control analysis of haplotypes showed a significant association in males only. G-M2+-S1 conferred risk for gallstone disease (P=0.036; OR 1.593, 95% CI 1.029 to 2.464), while A-M2+-S1 was protective (P=0.002; OR 0.370, 95% CI 0.197 to 0.695) against gallstone disease. InAPOA1−75-APOA1+83bilocus haplotypes, G-M2+was associated (P=0.0001) with very high risk (OR 3.173, 95% CI 1.774 to 5.674) for gallstone disease in males only.APOA1−75-APOC3SstIhaplotypes also showed significant association whileAPOA1+83-APOC3SstIhaplotypes showed no association with gallstone disease.CONCLUSIONS: TheAPOA1−75 G/A polymorphism is associated with gallstone disease and shows sex-specific differences. On the other hand,APOA1M2+/−andAPOC3 SstIpolymorphisms may not be associated with gallstone disease. Haplotype analysis is a better predictor of risk for gallstone disease.

scholarly journals Haplotype analysis suggests a single Balkan origin for the Gaucher disease [D409H;H255Q] double mutant allele

2008 ◽  
Vol 29 (6) ◽  
pp. E58-E67 ◽  
Author(s):  
Raül Santamaria ◽  
Helen Michelakakis ◽  
Marina Moraitou ◽  
Evangelia Dimitriou ◽  
Silvia Dominissini ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Mutant Allele ◽  
Double Mutant ◽  
Haplotype Analysis

No Involvement of the Calcium Channel Gene (CACNA1A) in a Family with Cluster Headache

Cephalalgia ◽  
2001 ◽  
Vol 21 (10) ◽  
pp. 959-962 ◽  
Author(s):  
J Haan ◽  
JA van Vliet ◽  
EE Kors ◽  
GM Terwindt ◽  
FLMG Vermeulen ◽  
...  
Keyword(s):  
Cluster Headache ◽  
Calcium Channel ◽  
Haplotype Analysis ◽  
Genetic Factors ◽  
Sscp Analysis ◽  
Causative Mutation ◽  
Extended Pedigree ◽  
Channel Gene ◽  
Disease Haplotype ◽  
Cacna1a Gene

It is very likely that genetic factors play a role in the pathophysiology of cluster headache (CH). As CH shares its paroxysmal character with migraine, and migraine has been described in coexistence with CH in some families, we hypothesized that both diseases might share a genetic aetiology. In this study, we tested whether the migraine CACNA1A gene on chromosome 19 is involved in CH in an extended pedigree. Haplotype analysis did not reveal an obvious disease haplotype, and SSCP analysis of all 47 exons of the CACNA1A gene did not reveal a causative mutation. CH in this family is not caused by mutations in the CACNA1A gene.

New Insights into the Origin of the Gaucher Disease-Causing Mutation N370S: Extended Haplotype Analysis Using the 5GC3.2, 5470 G/A, and ITG6.2 Polymorphisms

2001 ◽  
Vol 27 (5) ◽  
pp. 950-959 ◽  
Author(s):  
Adriana Rodrı́guez-Marı́ ◽  
Anna Dı́az-Font ◽  
Amparo Chabás ◽  
Gregory M. Pastores ◽  
Daniel Grinberg ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Haplotype Analysis ◽  
Extended Haplotype

scholarly journals Recurrence of the D409H mutation in Spanish Gaucher disease patients: description of a new homozygous patient and haplotype analysis.

1998 ◽  
Vol 35 (9) ◽  
pp. 775-777 ◽  
Author(s):  
A Chabas ◽  
L Gort ◽  
M Montfort ◽  
F Castello ◽  
M C Dominguez ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Haplotype Analysis ◽  
Homozygous Patient

scholarly journals The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Yoo-Mi Kim ◽  
Jin-Ho Choi ◽  
Gu-Hwan Kim ◽  
Young Bae Sohn ◽  
Jung Min Ko ◽  
...  
Keyword(s):  
Founder Effect ◽  
Gaucher Disease ◽  
Clinical Characteristics ◽  
Haplotype Analysis ◽  
Study Cohort ◽  
Ashkenazi Jewish ◽  
Founder Effects ◽  
Neuroprotective Effects ◽  
Shared Haplotype

Abstract Background Gaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA. Haplotype analyses previously demonstrated founder effects for particular GBA mutations in Ashkenazi Jewish and French-Canadian populations. This study aimed to investigate the clinical characteristics and mutation spectrum of GBA in Korean GD patients and to identify founder effect of GBA p.G85E in non-neuronopathic GD patients. Results The study cohort included 62 GD patients from 58 unrelated families. Among them, 18 patients from 17 families harbored the p.G85E mutation. Haplotype analysis was performed for 9 probands and their parents for whom DNA samples were available. In 58 unrelated probands, the GBA mutation p.L483P was the most common (30/116 alleles, 26%), followed by p.G85E (16%), p.F252I (13%), and p.R296Q (9%). The median age at diagnosis of the 18 patients harboring the p.G85E mutation was 3.8 (range 1.2–57) years. No patients developed neurological symptoms during follow-up periods of 2.2–20.3 (median 13.9) years. The size of the shared haplotype containing GBA p.G85E was 732 kbp, leading to an estimated age of 3075 years. Conclusion The GBA p.G85E mutation, which appears to be neuroprotective despite producing distinctive visceromegaly and skeletal symptoms, exhibited a potential founder effect in Korean GD patients.

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