Fabry disease: Evidence for a regional founder effect of the GLA gene mutation 30delG in Brazilian patients

Alencar, Dayse O.; Netto, Cristina Brinckmann Oliveira; Ashton‐Prolla, Patrícia; Giugliani, Roberto; Ribeiro-dos-Santos, Ândrea; Pereira, Fernanda Alves Cangerana; Matte, Úrsula da Silveira; Santos, Ney Pereira Carneiro dos; Santos, Sidney Emanuel Batista dos

doi:10.1016/j.ymgmr.2014.09.002

Cited by 4 publications

(2 citation statements)

References 36 publications

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“…Most of the GLA gene variants (identified by us) are specific to single families, which in general is a typical feature of X-linked diseases, and FD in particular [34]. Only 17 (16.4%) GLA variants were identified in two or more families with FD, while each of the remaining variants was detected in members of the same family.…”

Section: Resultsmentioning

confidence: 85%

Genotype–Phenotype Correlations in 293 Russian Patients with Causal Fabry Disease Variants

Savostyanov,

Pushkov,

Zhanin

et al. 2023

Genes

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Background: Fabry disease (FD) is a rare hereditary multisystem disease caused by variants of the GLA gene. Determination of GLA gene variants and identification of genotype–phenotype correlations allow us to explain the features of FD associated with predominant damage of one or another system, both in the classical and atypical forms of FD, as well as in cases with late manifestation and involvement of one of the systems. Methods: The study included 293 Russian patients with pathogenic variants of the GLA gene, which were identified as a result of various selective screening programs. Screening was carried out for 48,428 high-risk patients using a two-step diagnostic algorithm, including the determination of the concentration of the biomarker lyso-Gb3 as a first-tier test. Screening of atypical FD among patients with HCM was carried out via high-throughput sequencing in another 2427 patients. Results: 102 (0.20%) cases of FD were identified among unrelated patients as a result of the study of 50,855 patients. Molecular genetic testing allowed us to reveal the spectrum and frequencies of 104 different pathogenic variants of the GLA gene in 293 examined patients from 133 families. The spectrum and frequencies of clinical manifestations in patients with FD, including 20 pediatric patients, were described. Correlations between the concentration of the lyso-Gb3 biomarker and the type of pathogenic variants of the GLA gene have been established. Variants identified in patients with early stroke were described, and the association of certain variants with the development of stroke was established. Conclusions: The results of a large-scale selective FD screening, as well as clinical and molecular genetic features, in a cohort of 293 Russian patients with FD are described.

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Section: Resultsmentioning

confidence: 85%

Genotype–Phenotype Correlations in 293 Russian Patients with Causal Fabry Disease Variants

Savostyanov,

Pushkov,

Zhanin

et al. 2023

Genes

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show abstract

“…This finding can be attributed to founder effects because this mutation was present in a small number of individuals from a large population due to low genetic variation (Morrone et al, 2014). Moreover, it has been reported that other genetic disorders with low worldwide prevalence are more frequent in some ethnic groups or populations with high consanguinity rates (de Alencar et al, 2014;Fiore et al, 2011;Kirov et al, 2019). The increase in inbreeding and increased sensitivity to genetic drift occurs when a new population is established by a small number of individuals (Kato et al, 1997;Wood et al, 2013;Yamada et al, 1998).…”

Section: Mps Is Characterized By Various Mutations In the Galns Genementioning

confidence: 99%

Molecular characterization of mucopolysaccharidosis type IVA patients in the Andean region of Colombia

Pachajoa

Acosta

Alméciga-Díaz

et al. 2021

American J of Med Genetics Pt C

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Colombia has a high prevalence of mucopolysaccharidosis (MPS) type IVA. Nevertheless, data regarding the mutation spectrum for MPS IVA in this population have not been completely characterized. Forty-seven families and 53 patients from seven different Colombian regions were tested for MPS IVA mutations. We compared the sequences with the N-acetylgalactosamine-6-sulfatase (GALNS) reference sequence NM_000512.4, and gene variants were reported. Bioinformatics analysis was performed using SWISS-MODEL. The mutant proteins were generated by homology from the wild-type GALNS 4FDJ template obtained from the PDB database, and visualization was performed using Swiss-PDBViewer and UCSF Chimera. The predictive analysis was run using different bioinformatic tools, and the deleterious annotation of genetic variants was performed using a neural network. We found that 79% and 21% of the cohort was homozygous and compound heterozygous, respectively. The most frequent mutation observed was p.Gly301Cys (78.3% of alleles), followed by p.Arg386Cys (10.4% of alleles). A novel mutation (p.Phe72Ile) was described and classified in silico as a pathogenic variant. This study reveals the mutation spectrum of MPS IVA in Colombia. The high prevalence of the p.Gly301Cys mutation suggests a founder effect of this variant in the Colombian population that causes diseases in the Andean region (via migration). These data can facilitate genetic counseling, prenatal diagnosis, and the design of therapeutic interventions.

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Identification of a SCN5A founder mutation causing sudden death, Brugada syndrome, and conduction blocks in Southern Italy

et al. 2021

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Fabry disease: Evidence for a regional founder effect of the GLA gene mutation 30delG in Brazilian patients

Cited by 4 publications

References 36 publications

Genotype–Phenotype Correlations in 293 Russian Patients with Causal Fabry Disease Variants

Genotype–Phenotype Correlations in 293 Russian Patients with Causal Fabry Disease Variants

Molecular characterization of mucopolysaccharidosis type IVA patients in the Andean region of Colombia

Identification of a SCN5A founder mutation causing sudden death, Brugada syndrome, and conduction blocks in Southern Italy

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