Ben Halim Nizar, Hsouna Sana, Lasram Khaled, Rejeb Insaf, Walha Asma, Talmoudi Faten, Messai Habib, Sabrine Ben Brick Ahlem, Ouragini Houyem, Cherif Wafa, Nagara Majdi, Ben Rhouma Faten, Chouchene Ibtissem, Ouechtati Farah, Bouyacoub Yosra, Ben Rekaya Mariem, Messaoud Olfa, Ben Ammar Slim, El Matri Leila, Tebib Neji, Ben Dridi Marie F, Mokni Mourad, Amouri Ahlem, Kefi Rym, Abdelhak Sonia
Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
Department of Histology and Cytogenetics, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
Am J Hum Biol. 2016 Mar-Apr;28(2):171-80. doi: 10.1002/ajhb.22764. Epub 2015 Jul 16.
Consanguinity is common in Tunisia. However, little information exists on its impact on recessive disorders. In this study, we evaluate the impact of consanguineous marriages on the occurrence of some specific autosomal recessive disorders and consider how other factors, such as population substructure and mutation frequency, may be of equal importance in disease prevalence.
Consanguinity profiles were retrospectively studied among 425 Tunisian patients suffering from autosomal recessive xeroderma pigmentosum, dystrophic epidermolysis bullosa, nonsyndromic retinitis pigmentosa, Gaucher disease, Fanconi anemia, glycogenosis type I, and ichthyosis, and compared to those of a healthy control sample.
Consanguinity was observed in 341 cases (64.94%). Consanguinity rates per disease were 75.63, 63.64, 60.64, 61.29, 57.89, 73.33, and 51.28%, respectively. First-cousin marriages were the most common form of consanguinity (48.94%) with the percentages of 55.46, 45.46, 47.87, 48.39, 45.61, 56.66, and 35.90%, respectively. A very high level of geographic endogamy was also observed (93.92%), with the values by disease ranging between 75.86 and 96.64%. We observed an overall excess risk associated to consanguinity of nearly sevenfold which was proportional to the number of affected siblings and the frequency of disease allele in the family. Consanguinity was significantly associated with the first five cited diseases (odds ratio = 24.41, 15.17, 7.5, 5.53, and 5.07, respectively). However, no meaningful effects were reported among the remaining diseases.
This study reveals a variation in the excess risk linked to consanguinity according to the type of disorder, suggesting the potential of cryptic population substructure to contribute to disease incidence in populations with complex social structure like Tunisia. It also emphasizes the role of other health and demographic aspects such as mutation frequency and reproductive replacement in diseases etiology.
近亲结婚在突尼斯很常见。然而，关于其对隐性疾病影响的信息却很少。在本研究中，我们评估近亲婚姻对某些特定常染色体隐性疾病发生的影响，并探讨其他因素，如人群亚结构和突变频率，在疾病流行中可能具有同等重要性。
对425名患有常染色体隐性遗传性色素性干皮病、营养不良性大疱性表皮松解症、非综合征性视网膜色素变性、戈谢病、范可尼贫血、I型糖原贮积病和鱼鳞病的突尼斯患者的近亲关系谱进行回顾性研究，并与健康对照样本进行比较。
在341例（64.94%）中观察到近亲关系。每种疾病的近亲结婚率分别为75.63%、63.64%、60.64%、61.29%、57.89%、73.33%和51.28%。表亲结婚是最常见的近亲结婚形式（48.94%），在各疾病中所占比例分别为55.46%、45.46%、47.87%、48.39%、45.61%、56.66%和35.90%。还观察到非常高的地理内婚率（93.92%），各疾病的该数值在75.86%至96.64%之间。我们观察到与近亲结婚相关的总体超额风险接近7倍，这与受影响兄弟姐妹的数量以及家庭中疾病等位基因的频率成正比。近亲结婚与前五种提及的疾病显著相关（比值比分别为24.41、15.17、7.5、5.53和5.07）。然而，在其余疾病中未报告有意义的影响。
本研究揭示了与近亲结婚相关的超额风险因疾病类型而异，这表明在像突尼斯这样具有复杂社会结构的人群中，隐性人群亚结构可能对疾病发病率有影响。它还强调了其他健康和人口统计学方面，如突变频率和生殖替代在疾病病因学中的作用。
