Brazil has 215 million inhabitants, a population with a high level of admixture and internal genetic variation of sampled populations (Carvalho-Silva DR, et al, 2001). Brazil’s health disparities exist amid the Southern versus Northern regions. The Northeast is an underdeveloped region with high rates of consanguinity, a practice brought by the so-called New Christians, or Jews, fleeing the Portuguese Catholic Inquisition. After the rise of the Iberian Union, Holland sent its military expeditions to conquer the Brazilian Northeast region, which is geographically strategic for the routes coming from Western Europe. the following 24 years of Dutch rule from 1630 to 1654 left marks on the architecture, culture, and heterogeneity of the Brazilian Northeast.

The region named Seridó, or Serid in Hebrew, means survivor, escaped, or even she'erit, refuge from Him or refuge from God. This region is in the Southern center of the State of Rio Grande do Norte, and has a series of unique features, both in terms of culture and geography. Recent genetic studies on inhabitants from the Seridó region show a predominance of rare genetic diseases and founder mutations.

Some examples of these are Berardinelli-Seip syndrome and spastic paraplegia, optic atrophy, and neuropathy (SPOAN), both autosomal recessive. Berardinelli-Seip syndrome, or Congenital Generalized Lipodystrophy (OMIM 269700), has a worldwide incidence of 1:10,000,000 (Van Maldergem et al. 2002). In the Seridó Region, it has a prevalence of 32.3:1,000,000 with more than 70 individuals diagnosed. SPOAN Syndrome (OMIM 609541) is a rare disease with a total of 68 individuals diagnosed in Brazil, 47 of whom are from Seridó. Those 68 patients belong to 43 sibships, 40 of which exhibit parental consanguinity. It is estimated that 1 in 15 inhabitants are heterozygous carriers of the mutation (Macedo-Souza et al. 2005).

I am investigating MUTYH-Associated Polyposis syndrome (MAP, OMIM 604933) an autosomal recessive predisposition syndrome to colon polyposis and colorectal cancer caused by biallelic pathogenic or likely pathogenic variants in the MUTYH gene. The two most commonly described MUTYH variants are the European founder variants c.536A>G (Y179C) and c.1187G>A (G396D). These two make up 50-82% of all MUTYH variants in those with a diagnosis of MAP. In our cohort of 157 individuals from Seridó, 63% are carriers of the Y179C variant. The most interesting aspect of this research project is drawing the pedigrees, where I typically start with one page and finish with three, documenting the high frequency of intermarriage in the families. All individuals in the study receive genetic counseling and are warned about the risk of carrying the pathogenic allele, given the high prevalence among this population.

One might think that genetic counseling should be an essential health service in this region. However, in Brazil, there are only ten genetic counseling services, mainly located in the Southern region. In 2009, genetic counseling was recognized as an essential health service by Brazil’s national public health system (Sistema Único de Saúde (SUS)), which is responsible for 75% of all Brazilians’ health. However, the system does not pay for most genetic tests, and private genetic testing costs between $300 and $700 for a gene panel and $800 for an exome. This is a stark contrast to the minimum monthly wage in Brazil, which is equivalent to approximately $249. The challenge is to decentralize genetic counseling services, but also to create training programs for health professionals and establish collaborative research projects between clinical centers and universities for a better understanding of genetics in Brazil.

 

References:

Carvalho-Silva, D.R., Santos, F.R., Rocha, J., Pena, S.D., 2001. The phylogeography of Brazilian Y-chromosome lineages. Am J Hum Genet. 68(1):281-6. doi: 10.1086/316931. Epub 2000 Nov 22. PMID: 11090340; PMCID: PMC1234928.

Van Maldergem, L., Magré, J., Khallouf, T.E., Gedde-Dahl, T., Delépine, M., Trygstad, O., et al, 2002. Genotype-phenotype relationships in Berardinelli-Seip congenital lipodystrophy. Journal of Medical Genetics. 39, 722–733. https://doi.org/10.1136/jmg.39.10.722.

Macedo-Souza, L.I., Kok, F., Santos, S., Amorim, S.C., Starling, A., Nishimura, A., et al, 2005. Spastic paraplegia, optic atrophy, and neuropathy is linked to chromosome 11q13. Annals of Neurology 57, 730–737. https://doi.org/10.1002/ana.20478.

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