Familial mediterranean fever mutation frequencies and carrier rates among a mixed Arabic population

Familial Mediterranean Fever [FMF] is an autoinflammatory periodic disorder characterized by febrile and painful attacks due to inflammation involving the serosal membranes. The gene implicated in this disorder, MEFV, has been cloned and mutations in its coding regions have been identified. We aimed at identifying the frequency of MEFV, mutations and carrier frequency in a mixed Arabic population. We identified 29 prob and s from 29 unrelated sibships segregating the disorder and representing the affected individual cohort. We screened 200 anonymous deoxyribonucleic acid [DNA] samples, representing a healthy adult cohort, for the mutations found to be common in the affected individual cohort. We also, screened anonymous DNA samples from 4 Arabic countries, namely, Egypt [231], Syria [225], Iraq [176] and the Kingdom of -Saudi Arabia [107] thus enlarging our healthy adult cohort. The study was carried out between 1999 and 2002 at Jordan University of Science and Technology, Irbid and the University of Jordan, Amman, Jordan. Out of the 58 alleles of the 29 prob and s, only 31 mutations were identified and M694V and V726A are the most common. The mutation E148Q was the most common among the healthy adult cohort, but was not present in affected individuals. The collective mutant allele frequency "q" was 0.101. The expected carrier rate was 18.1% [one in 5.5] while the observed carrier rate was 18.4% [one in 5.4]. E148Q has reduced penetrance and thus, a proportion of the individuals genetically affected with FMF remain asymptomatic. M694I and M680I are more prevalent in the affected individuals cohort, which points to their higher penetrance. The overall carrier rate is one in 5, but the selective heterozygote advantage could not be demonstrated in this study due to the relatively small sample size

Linkage analysis of a large inbred family with congenital megaloblastic anemia

Megaloblastic anemia during infancy and early childhood often reflects a hereditary disorder of cobalamin's absorption, transport, or intracellular metabolism. There are 3 well defined autosomal recessive syndromes manifesting with megaloblastic anemia due to defects in cobalamin absorption or transport, namely congenital pernicious anemia, Imerslund-Grasbeck syndrome and Transcobalamin II deficiency. The genes responsible for the 3 disorders are gene intrinsic factor [GIF], MGA1 and TCN2, as well as the gene for Transcobalamin I, TCN1 are mapped or cloned, or both. We describe the clinical picture of 7 patients from 3 sibships, belong to one large inbred family who presented with megaloblastic anemia during infancy. The mode of inheritance follows an autosomal recessive pattern and the syndrome was completely reversed by parentral vitamin B12 therapy. The ascertainment of the family was carried out in 1998 in the Princess Rhama Children's Hospital, which is affiliated with Jordan University of Science and Technology, Jordan. We performed linkage analysis in this family for genes or regions involved in the above mentioned disorders. The genes implicated in the etiology of the previously mentioned disorders were excluded from being responsible for the disorder in this family. The exclusion of the involvement of GIF, MGA1, TCN1 and TCN2 in this family suggests that another gene and its product, involved in cobalamin absorption or transport, remains to be identified. A genome-wide search of the gene implicated in this family may give some insight on that gene, and its function