Hémophilie B Leyden : les corrections naturelles d'un déficit temporaire de transcription

Abstract

An enzyme deficiency where a normal level of an abnormal protein is accounted for by a mutation within a coding region of the corresponding gene is common place in human pathology. Thus, hemophilia B which involves mutations in the coagulation factor IX gene, most often results from deleterious amino-acid changes in the protein sequence. In other, more limited, instances, and enzyme deficiency is accounted for by a mutation in a regulatory region of a gene or a noncoding region of its transcript. These mutations eventually result in a poor transcription or translation efficiency which is responsible for a low level of a normal protein. A further situation involves a unique step where a weakened transcription, induced by a mutation in a regulatory region of a gene, is secondarily restored to a (sub)normal level by the late appearance of development-associated transcription factor(s). This is examplified by the so-called Leyden phenotype, a rare case of transient haemophilia B. The patients suffering from this disease first present with bleeding disorders and a marked deficiency of a normal factor IX in plasma. However, after puberty they gradually recover from the disease as the plasma factor IX level increases to a sub-normal level. A testosterone-induced triggering of a mutated promoter in the factor IX gene accounts for this phenotype.