Differential impact of consanguineous marriages on autosomal recessive diseases in Tunisia

Nizar Ben Halim (1) , Sana Hsouna (1) , Khaled Lasram (1) , Insaf Rejeb (1) , Asma Walha (1) , Faten Talmoudi (1, 2) , Habib Messai (1) , Ahlem Sabrine Ben Brick (1) , Houyem Ouragini (1) , Wafa Cherif (1) , Majdi Nagara (1) , Faten Ben Rhouma (1) , Ibtissem Chouchene (3) , Farah Ouechtati (1) , Yosra Bouyacoub (1) , Mariem Ben Rekaya (1) , Olfa Messaoud (1) , Slim Ben Ammar (2) , Leila El Matri (3) , Neji Tebib (4) , Marie F. Ben Dridi (4) , Mourad Mokni (5) , Ahlem Amouri (1, 2) , Rym Kefi (1) , Sonia Abdelhak (1)

1 LR11IPT05 - Laboratoire de Génomique Biomédicale et Oncogénétique - Biomedical Genomics and Oncogenetics Laboratory
2 Institut Pasteur de Tunis
3 Unité de recherche d'oculogénétique, Service B
4 Département de Pédiatrie, Unité des maladies métaboliques héréditaires
5 Service de dermatologie

Objectives 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. Methods 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. Results 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. Conclusions 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. (c) 2015 Wiley Periodicals, Inc.

Domaines: Sciences du Vivant [q-bio]; Génétique humaine

Nizar Ben Halim, Sana Hsouna, Khaled Lasram, Insaf Rejeb, Asma Walha, et al.. Differential impact of consanguineous marriages on autosomal recessive diseases in Tunisia. American Journal of Human Biology, 2016, 28 (2), pp.171 - 180. ⟨10.1002/ajhb.22764⟩. ⟨pasteur-01374977⟩