Cardoso-Dos-Santos Augusto César, Mariath Luiza Monteavaro, Trapp Franciele, Facchin Ana Carolina Brusius, Leistner Sandra, Kubaski Francyne, Giugliani Roberto, Schuler-Faccini Lavinia, Ribeiro Erlane Marques
Instituto Nacional de Ciência e Tecnologia de Genética Médica Populacional (INaGeMP), Porto Alegre, RS, Brazil.
Postgraduate Program in Genetics and Molecular Biology, Department of Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
J Community Genet. 2024 Oct;15(5):573-580. doi: 10.1007/s12687-024-00718-7. Epub 2024 Aug 19.
Geographic and sociodemographic aspects may influence the natural history and epidemiology of mucopolysaccharidoses (MPS). The main objective in this work was to evaluate the clinical, molecular, and geographic profile of MPS in a population from Ceará (Northeast Brazil). For this, we have performed a descriptive cross-sectional study based on clinical evaluation, interviews with patients and/or family members, and review of medical records of 76 MPS patients. MPS II was the most common type, with the most affected individuals presenting missense pathogenic variants. Patients with MPS I proved to be the most severe clinical phenotype, presenting the first symptoms (mean: 7.1 months; SD = 4.5) and being diagnosed earlier (2.2 years; SD = 2.1) in comparison with the other types. In addition, we have shown that 13 individuals with MPS VI were born of consanguineous marriages in small, nearby cities, in a place where geographical isolation, consanguinity, and clusters of genetic diseases were previously reported. Ten of these individuals (at least, seven different families) presented a rare pathogenic variant in the ARSB gene, c.1143-8T > G in homozygosity, previously reported only among Iberian and South American patients. The results presented here provide a comprehensive picture of MPS in an important state of the Brazilian Northeast, a region that concentrates many risk factors for rare genetic diseases, such as endogamy, inbreeding, and reproductive isolation. We discuss the possible evolutionary processes and biosocial dynamics that can help to explain this finding in terms of population medical genetics and public health.
地理和社会人口学因素可能会影响黏多糖贮积症（MPS）的自然病史和流行病学特征。本研究的主要目的是评估巴西东北部塞阿拉州人群中MPS的临床、分子和地理特征。为此，我们基于临床评估、对患者和/或家庭成员的访谈以及对76例MPS患者病历的回顾，开展了一项描述性横断面研究。MPS II是最常见的类型，受影响最严重的个体存在错义致病变异。与其他类型相比，MPS I患者的临床表型最为严重，最早出现症状（平均：7.1个月；标准差=4.5），且诊断较早（2.2岁；标准差=2.1）。此外，我们发现13例MPS VI患者出生于附近小城市的近亲婚姻家庭，此前该地区曾报告存在地理隔离、近亲结婚和遗传病聚集现象。其中10例个体（至少来自7个不同家庭）在ARSB基因中呈现一种罕见的纯合致病变异，即c.1143-8T＞G，此前仅在伊比利亚和南美患者中报道过。本文呈现的结果全面描绘了巴西东北部一个重要州的MPS情况，该地区集中了许多罕见遗传病的风险因素，如族内通婚、近亲繁殖和生殖隔离。我们讨论了可能的进化过程和生物社会动态，有助于从群体医学遗传学和公共卫生角度解释这一发现。
