ARSA-PD associated alleles in the Portuguese population: frequency determination and haplotype analysis

Marcão, Ana; Pinto, Eugénia; Rocha, Sónia; Sá-Miranda, Clara; Ferreira, Luis Mariano; Amaral, Olga

doi:10.1016/s1096-7192(03)00092-1

Cited by 4 publications

(2 citation statements)

References 7 publications

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“…Furthermore, there are many reports on the pseudodeficiency alleles on arylsulfatase A (ARSA), an enzyme responsible for metachromatic leukodystrophy [25], [26]. In the case of ARSA, subsequent evidences have shown that there are many pseudodeficiency mutations that are not limited to a restricted area but are global [27], [28]. In fact, its number is still increasing these days [29], [30].…”

Section: Discussionmentioning

confidence: 99%

Enzyme activities of α-glucosidase in Japanese neonates with pseudodeficiency alleles

Mashima

Okuyama

2017

Molecular Genetics and Metabolism Reports

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Lysosomal storage disorders (LSDs) are caused by defective enzyme activities in lysosomes, characterized by the accumulation of sphingolipids, glycolipids, oligosaccharides, mucopolysaccharides, the oxidation products of cholesterol, and other biological substances. A growing number of clinical studies have suggested the enhanced efficacy of existing therapies, including enzyme replacement therapy, which is effective when it is initiated during the presymptomatic period. Thus, the identification of disease-affected individuals by newborn screening has been considered an effective platform. Previous studies have suggested that the discrimination of infantile-onset Pompe disease (IOPD) requires multi-step examination of GAA enzyme activity using the fluorometric technique. In sharp contrast, the MS/MS-based technique can identify the population of IOPD and the pseudodeficiency alleles of the GAA enzyme [Liao HC et al. Clin Chem (2017) in press; doi: http://dx.doi.org/10.1373/clinchem.2016.269027]. To determine whether MS/MS-based assay can identify these two populations in Japanese neonates, we first performed a validation study of this assay using flow-injection analysis (FIA)-MS/MS and liquid chromatography (LC)-MS/MS followed by examination of GAA enzyme activity in our population. By minimizing the effect of substrate-derived in-source decomposition products, the activities of 6 LSD enzymes were quantified in FIA-MS/MS and LC-MS/MS. The mean value of GAA activity with IOPD, pseudodeficiency alleles, and healthy controls by FIA-MS/MS were 1.0 ± 0.3 μmol/h/L (max, 1.3; min, 0.7; median, 1.2; n = 3), 2.7 ± 0.7 μmol/h/L (max, 4.5; min, 1.5; median, 2.5; n = 19), and 12.9 ± 5.4 μmol/h/L (max, 29.6; min, 2.5; median, 11.0; n = 83), respectively. These results suggest that the population of GAA with pseudodeficiency alleles has approximately 20% of GAA enzyme activity compared to controls, providing the preliminary evidence to estimate the cut-off values in the Japanese population using this technique.

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Section: Discussionmentioning

confidence: 99%

Enzyme activities of α-glucosidase in Japanese neonates with pseudodeficiency alleles

Mashima

Okuyama

2017

Molecular Genetics and Metabolism Reports

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“…Carriers for metachromatic leukodystrophy have been shown to have low arylsulfatase A (ARSA) activity, which has been strongly associated with neuropsychiatric features, including SSD and psychosis; specifically, heterozygous carriers for the ARSA I179S variant present with a psychiatric onset of metachromatic leukodystrophy which can mirror SSD, in addition to presenting with dementia and neurological phenotypes (e.g. paraparesis) (Demily et al, 2014;Ługowska et al, 2005;Marcão et al, 2003). Multiple studies have shown an enrichment for NPC carriers within psychiatric populations (Bauer et al, 2013;Maubert et al, 2013Maubert et al, , 2015.…”

Section: Prevalence Of Treatable Genetic Disorder Variants Within the Study Cohortmentioning

confidence: 99%

When rare meets common: Treatable genetic diseases are enriched in the general psychiatric population

Sriretnakumar

Harripaul

Kennedy

et al. 2021

Preprint

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Mental illnesses are one of the biggest contributors to the global disease burden. Despite the increased recognition, diagnosis and ongoing research of mental health disorders, the etiology and underlying molecular mechanisms of these disorders are yet to be fully elucidated. Moreover, despite many treatment options available, a large subset of the psychiatric patient population is non-responsive to standard medications and therapies. There has not been a comprehensive study to date examining the burden and impact of treatable genetic disorders (TGDs) that can present with neuropsychiatric features in psychiatric patient populations. In this study, we test the hypothesis that TGDs that present with psychiatric symptoms are more prevalent within psychiatric patient populations compared to the general population by performing targeted next-generation sequencing (NGS) of 129 genes associated with 108 TGDs in a cohort of 2301 psychiatric patients. In total, 72 putative affected and 293 putative carriers for TGDs were identified, with known or likely pathogenic variants in 78 genes. Despite screening for only 108 genetic disorders, this study showed an approximately four-fold (4.13%) enrichment for genetic disorders within the psychiatric population relative to the estimated 1% cumulative prevalence of all single gene disorders globally. This strongly suggests that the prevalence of these, and most likely all, genetic diseases are greatly underestimated in psychiatric populations. Increasing awareness and ensuring accurate diagnosis of TGDs will open new avenues to targeted treatment for a subset of psychiatric patients.

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Determination of arylsulfatase A pseudodeficiency allele and haplotype frequency in the Tunisian population

et al. 2015

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Arylsulfatase A (ASA) is a lysosomal enzyme involved in the catabolism of cerebroside sulfate. ASA deficiency is associated with metachromatic leukodystrophy (MLD). Low ASA activities have also been reported in a more common condition with no apparent clinical consequences termed ASA pseudo-deficiency (ASA-PD) which is associated with two linked mutations in the ASA gene (c.1049A>G and c.*96A>G). This study aimed to investigate the frequency of the two ASA-PD variants and their linkage disequilibrium (LD) among Tunisians. ASA-PD variants were detected in 129 healthy Tunisians and their frequencies were compared to those described worldwide. The frequency of the PD allele was estimated at 17.4% for the overall sample, with c.1049A>G and c.*96A>G frequencies of 25.6 and 17.4%, respectively. This study also revealed a high LD between the two ASA-PD variants (r(2) = 0.61). Inter-population analysis revealed similarities in the ASA-PD genetic structure between Tunisians and populations from Middle East with c.*96A>G frequencies being the highest in the world. A significant North vs. South genetic differentiation in the ASA-PD frequency was also observed in Tunisian population who seems genetically intermediate between Africans, Middle-Easterners and Europeans. This is the first report on the allele frequency of the ASA-PD in North Africa, revealing a relatively high frequency of the PD allele among Tunisians. This study gives also evidence on the importance of discriminating ASA-PD allele from pathological mutations causing MLD and supporting enzymatic activity testing with both sulfatiduria determination and genetic testing in the differential diagnosis of MLD in the Tunisian population.

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ARSA-PD associated alleles in the Portuguese population: frequency determination and haplotype analysis

Cited by 4 publications

References 7 publications

Enzyme activities of α-glucosidase in Japanese neonates with pseudodeficiency alleles

Enzyme activities of α-glucosidase in Japanese neonates with pseudodeficiency alleles

When rare meets common: Treatable genetic diseases are enriched in the general psychiatric population

Determination of arylsulfatase A pseudodeficiency allele and haplotype frequency in the Tunisian population

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