A Community-Based Study of Mucopolysaccharidosis Type VI in Brazil: The Influence of Founder Effect, Endogamy and Consanguinity

Costa-Motta, Fabiana Moura; Bender, Fernanda; Acosta, Angelina Xavier; Abe‐Sandes, Kiyoko; Machado, Taisa Manuela Bonfim; Bomfim, Thais Ferreira; Sorte, Tatiana Boa; Silva, Danniel da; Bittles, Alan H.; Giugliani, Roberto; Leistner-Segal, Sandra

doi:10.1159/000358404

Cited by 34 publications

(36 citation statements)

References 22 publications

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“…Most patients with a history of consanguinity were from the Southeast and Northeast regions. In the latter, previous studies have reported high rates of consanguinity in specific areas of such states as Bahia (Costa‐Motta et al, ), Paraíba (Weller et al, ) e Rio Grande do Norte (Santos et al, ). According to a March of Dimes report, an estimated 1 to 10% of unions in South America are consanguineous (Christianson, Howson, & Modell, ), a rate far below that found in the present study and in the aforementioned investigations.…”

Section: Discussionmentioning

confidence: 95%

Estimated birth prevalence of mucopolysaccharidoses in Brazil

Federhen

Pasqualim

Freitas

et al. 2020

American J of Med Genetics Pt A

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Several studies have been published on the frequency of the mucopolysaccharidoses (MPS) in different countries. The objective of the present study was to estimate the birth prevalence (BP) of MPS in Brazil. MPS diagnosis registered at MPS‐Brazil Network and in Instituto Vidas Raras were reviewed. BP was estimated by (a) the number of registered patients born between 1994 and 2015 was divided by the number of live births (LBs), and (b) a sample of 1,000 healthy individuals was tested for the most frequent variant in IDUA gene in MPS I (p.Trp402Ter) to estimate the frequency of heterozygosity and homozygosity. (a) The BP based on total number of LBs was (cases per 100,000 LBs): MPS overall: 1.25; MPS I: 0.24; MPS II: 0.37; MPS III: 0.21; MPS IV: 0.14; MPS VI: 0.28; MPS VII: 0.02. (b) The overall frequency of p.Trp402Ter was 0.002. Considering the frequency of heterozygotes for the p.Trp402Ter IDUA variant in the RS state, the frequency of this variant among MPS I patients and the relative frequency of the different MPSs, we estimated the birth prevalence of MPS in total and of each MPS type, as follows: MPS overall: 4.62; MPS I: 0.95; MPS II: 1.32; MPS III: 0.56; MPS IV: 0.57; MPS VI: 1.02; MPS VII: 0.05. This study provided original data about BP and relative frequency of the MPS types, in Brazil, based on the frequency of the commonest IDUA pathogenic variant and in the records of two large patient databases.

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Section: Discussionmentioning

confidence: 95%

Estimated birth prevalence of mucopolysaccharidoses in Brazil

Federhen

Pasqualim

Freitas

et al. 2020

American J of Med Genetics Pt A

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“…Lastly, all 14 homozygote subjects with the variant p.(His178Leu) are Brazilian, and belong to a cluster of MPS VI patients living in Northeast Brazil. These subjects all show the same haplotype (Costa‐Motta et al., ), which is likely due to a founder effect, with the contemporary presence of parental consanguinity and endogamy.…”

Section: Variantsmentioning

confidence: 90%

“…The prevalence of MPS VI varies among populations, with estimates ranging from 0.0132 per 100,000 live births in Poland to 8.0 per 100,000 live births in Saudi Arabia to 20.0 per 100,000 live births in Monte Santo, a small town in Brazil (Costa‐Motta et al., ; Jurecka, Ługowska, Golda, Czartoryska, & Tylki‐Szymańska, ; Moammar, Cheriyan, Mathew, & Al‐Sannaa, ; Vairo et al., ). While several variables likely influence prevalence rates across populations, it is expected that populations with higher degrees of consanguinity display a higher prevalence of the disease (Baehner et al., ; Costa‐Motta et al., ). Importantly, disease prevalence is likely underestimated in all populations since these epidemiological studies generally rely on clinical identification of disease rather than prenatal or newborn screening (Valayannopoulos et al., ).…”

Section: Introductionmentioning

confidence: 99%

Mucopolysaccharidosis type VI (MPS VI) and molecular analysis: Review and classification of published variants in theARSBgene

et al. 2018

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Maroteaux–Lamy syndrome (MPS VI) is an autosomal recessive lysosomal storage disorder caused by pathogenic ARSB gene variants, commonly diagnosed through clinical findings and deficiency of the arylsulfatase B (ASB) enzyme. Detection of ARSB pathogenic variants can independently confirm diagnosis and render genetic counseling possible. In this review, we collect and summarize 908 alleles (201 distinct variants, including 3 polymorphisms previously considered as disease‐causing variants) from 478 individuals diagnosed with MPS VI, identified from literature and public databases. Each variant is further analyzed for clinical classification according to American College of Medical Genetics and Genomics (ACMG) guidelines. Results highlight the heterogeneity of ARSB alleles, with most unique variants (59.5%) identified as missense and 31.7% of unique alleles appearing once. Only 18% of distinct variants were previously recorded in public databases with supporting evidence and clinical significance. ACMG recommends publishing clinical and biochemical data that accurately characterize pathogenicity of new variants in association with reporting specific alleles. Variants analyzed were sent to ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/), and MPS VI locus‐specific database (http://mps6-database.org) where they will be available. High clinical suspicion coupled with diagnostic testing for deficient ASB activity and timely submission and classification of ARSB variants with biochemical and clinical data in public databases is essential for timely diagnosis of MPS VI.

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“…Hastalık klinik olarak heterojendir. Hastaların çoğunda hızlı ilerleyen form mevcut iken, az bir kısmında ise yavaş ilerleyen form mevcuttur (4). Yapılan uluslararası çalışmalarda, MPS tip VI insidansının Almanya'da yaşayan Türk toplumunda 1: 43,261, İsveç'te 1: 1,505,160 arasında değişen oranlarda olduğu belirtilmiştir (5).…”

Section: Introductionunclassified

“…Brezilya'da ve Brezilya'ya pek çok kişinin göç ettiği Portekiz'de, genel MPS dağılımı düşünüldüğünde, MPS tip VI'nın oransal olarak arttığı rapor edilmiştir (7,8). Örnek olarak; Brezilya'nın Monte Carlo şehrine bağlı Bahia eyaletinde, MPS VI prevelansı 1: 5,000 olarak yayınlamış ve bunun sebebi muhtemelen tüm olgularda tek mutasyonun varlığı (p.H178L) ve kabile içi evlenmenin kombinasyonu olarak gösterilmiş (4).…”

Section: Introductionunclassified