A novel mutation in the albumin gene (c.1A %26gt; C) resulting in analbuminemia

作者：Caridi Gianluca; Dagnino Monica; Lugani Francesca; Shalev Stavit A; Campagnoli Monica; Galliano Monica; Spiegel Ronen; Minchiotti Lorenzo^*

来源：European Journal of Clinical Investigation, 2013, 43(1): 72-78.

DOI：10.1111/eci.12019

• Analbuminemia
• DNA sequence
• Druze community
• human serum albumin
• missense mutation
• start codon

Background Analbuminemia (OMIM # 103600) is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating serum albumin in homozygous or compound heterozygous subjects. The trait is caused by a variety of mutations within the albumin gene. %26lt;br%26gt;Design We report here the clinical and molecular characterisation of two new cases of congenital analbuminemia diagnosed in two members of the Druze population living in a Galilean village (Northern Israel) on the basis of their low level of circulating albumin. The albumin gene was screened by single-strand conformation polymorphism and heteroduplex analysis, and the mutated region was submitted to DNA sequencing. %26lt;br%26gt;Results Both the analbuminemic subjects resulted homozygous for a previously unreported c.1A %26gt; C transversion, for which we suggest the name Afula from the hospital where the two cases were investigated. This mutation causes the loss of the primary start codon ATG for Met1, which is replaced by a - then untranslated - triplet CTG for Leu. (p.Met1Leu). The use of an alternative downstream ATG codon would probably give rise to a completely aberrant polypeptide chain, leading to a misrouted intracellular transport and a premature degradation. %26lt;br%26gt;Conclusions The discovery of this new ALB mutation, probably inherited from a common ancestor, sheds light on the molecular mechanism underlying the analbuminemic trait and may serve in the development of a rapid genetic test for the identification of a-symptomatic heterozygous carriers in the Druze population in the Galilee.

• 出版日期2013-1