XmnI Polymorphism in Sickle Cell Disease in North Morocco.

Sickle cell disease is one of the most common severe monogenic disorders in the world. The -158 XmnI polymorphism (C>T) of the Gγ-globin gene promoter is known to be associated with increased expression of the Gγ-globin gene, thus, higher production of Hb F and lesser clinical severity. This study aims to determine the frequency of the XmnI polymorphism and its association with Hb F levels as a modulating factor of sickle cell disease severity in north Moroccan patients. Three hundred and eight subjects carrying the sickle cell mutation and 160 healthy individuals were recruited at the regional hospital of Larache, Morocco. The complete blood count and the Hb F levels were analyzed. The XmnI polymorphism was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and statistical analysis were done using the Statistical Package for Social Sciences software version 20. Our results estimated the allelic frequency of the XmnI polymorphism in our population at 15.8%. Out of 468 samples, 7.6% were homozygous [+/+] and 16.4% were heterozygous [+/-] for the XmnI polymorphism. This polymorphism was revealed at 20.6% in SS patients, 24.2% in AS carriers, 28.6% in Hb S (HBB: c.20A>T)/ß-thalassemia (ß-thal) patients and 22.5% in AA subjects. The north Moroccan sickle cell disease patients have shown a low frequency of the XmnI polymorphism. This was later found to be associated with high Hb F levels and mild clinical severity.

Hemoglobinopathies in the North of Morocco: Consanguinity Pilot Study.

Consanguinity is a social behavior characterized by the arrangement of marriages between relatives. It coincides generally with the geographic distribution of recessive genetic diseases as it increases the likelihood of homozygosis and, consequently, the incidence of their pathologies in the population. In this pilot study, we assess the effect of inbreeding on the burden of hemoglobinopathies in Northern Morocco. From January 2016 to December 2018, 197 children born in the studied region to three ancestral generations and diagnosed with hemoglobinopathies were subject to investigation. The rate of consanguinity in the parents' generation of children with hemoglobinopathies was 50.25%, with first cousin marriages accounting for 68.69% of consanguineous unions (FI = 0.02). The corresponding rates in the general population, based on a sample of N = 900, were 29.67% and 82.02%, respectively. The marriages between first cousins are the most common among the other types of consanguineous unions. Our study propounds that consanguinity substantially contributes to the hemoglobinopathy burden in the studied region and has changed little over time. Refraining from consanguineous marriages and detecting couples at risk could contribute to the reduction of the incidence of genetic diseases in our country.

Alpha-Thalassemia in North Morocco: Prevalence and Molecular Spectrum.

Unlike the other hemoglobinopathies, few researches have been published concerning α-thalassemia in Morocco. The epidemiological features and the mutation spectrum of this disease are still unknown. This regional newborn screening is the first to study α-thalassemia in the north of Morocco. During the period from January 2015 to December 2016, 1658 newborns umbilical blood samples were investigated. Suspected newborns were screened for α-globin defects using Gap-PCR and Multiplex Ligation-dependent Probe Amplification technique. The prevalence of α-thalassemia, its mutation spectrum, and its allelic frequencies were described for the first time in Morocco. Six different α-globin genetic disorders were detected in 16 neonates. This screening valued the prevalence of α-thalassemia in the studied population at 0.96% and showed the wide mutation spectrum and the heterogeneous geographical distribution of the disease. A high rate of carriers was observed in Laouamra, a rural commune in Larache province. Heterogeneity of α-globin alleles in Morocco explains the high variability of α-thalassemia severity. This diversity reflects the anthropological history of the country. These results would contribute to the prevention of thalassemia in Morocco directing the design of a nationwide screening strategy and awareness campaign.