title: Differential impact of consanguineous marriages on autosomal recessive diseases in Tunisia.
abstract: OBJECTIVE
  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.
authors.affiliation: Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Nizar
authors.initials: N
authors.lastname: Ben Halim
authors.affiliation: Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Sana
authors.initials: S
authors.lastname: Hsouna
authors.affiliation: Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Khaled
authors.initials: K
authors.lastname: Lasram
authors.affiliation: Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Insaf
authors.initials: I
authors.lastname: Rejeb
authors.affiliation: Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Asma
authors.initials: A
authors.lastname: Walha
authors.affiliation: 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.
authors.forename: Faten
authors.initials: F
authors.lastname: Talmoudi
authors.affiliation: Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Habib
authors.initials: H
authors.lastname: Messai
authors.affiliation: Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Ahlem
authors.initials: A
authors.lastname: Sabrine Ben Brick
authors.affiliation: Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Houyem
authors.initials: H
authors.lastname: Ouragini
authors.affiliation: Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Wafa
authors.initials: W
authors.lastname: Cherif
authors.affiliation: Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Majdi
authors.initials: M
authors.lastname: Nagara
authors.affiliation: Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Faten
authors.initials: F
authors.lastname: Ben Rhouma
authors.affiliation: Oculogenetics Research Unit, Hedi Rais Institute of Ophthalmology, Tunis, 1006, Tunisia.
authors.forename: Ibtissem
authors.initials: I
authors.lastname: Chouchene
authors.affiliation: Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Farah
authors.initials: F
authors.lastname: Ouechtati
authors.affiliation: Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Yosra
authors.initials: Y
authors.lastname: Bouyacoub
authors.affiliation: Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Mariem
authors.initials: M
authors.lastname: Ben Rekaya
authors.affiliation: Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Olfa
authors.initials: O
authors.lastname: Messaoud
authors.affiliation: Clinical Biochemistry Laboratory, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Slim
authors.initials: S
authors.lastname: Ben Ammar
authors.affiliation: Oculogenetics Research Unit, Hedi Rais Institute of Ophthalmology, Tunis, 1006, Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: El Matri
authors.affiliation: Pediatric Department, La Rabta Hospital, Jebbari, 1007, Tunis, Tunisia.
authors.forename: Neji
authors.initials: N
authors.lastname: Tebib
authors.affiliation: Pediatric Department, La Rabta Hospital, Jebbari, 1007, Tunis, Tunisia.
authors.forename: Marie F
authors.initials: MF
authors.lastname: Ben Dridi
authors.affiliation: Department of Dermatology, La Rabta Hospital, Jebbari, 1007, Tunis, Tunisia.
authors.forename: Mourad
authors.initials: M
authors.lastname: Mokni
authors.affiliation: 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.
authors.forename: Ahlem
authors.initials: A
authors.lastname: Amouri
authors.affiliation: Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Rym
authors.initials: R
authors.lastname: Kefi
authors.affiliation: Biomedical Genomic and Oncogenetics Laboratory Lr11ipt05, Institut Pasteur de Tunis, Tunis, 1002, Tunisia.
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D014416:Tunisia / Q000453:epidemiology; D055815:Young Adult