Hypomorphic mutations of SEC23B gene account for mild phenotypes of congenital dyserythropoietic anemia type II

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• 作者：Roberta Russo^a ; ^b ; Concetta Langella^a ; ^b ; Maria Rosaria Esposito^b ; Antonella Gambale^b ; Francesco Vitiello^a ; ^b ; Fara Vallefuoco^b ; Torben Ek^c ; Elizabeth Yang^d ; Achille Iolascon^a ; ^b ; ^{achille.iolascon@unina.it}
• 关键词：CDA II ; SEC23B ; Hypomorphic mutations ; Genotype&ndash ; phenotype correlation
• 刊名：Blood Cells, Molecules, and Diseases
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：51
• 期：1
• 页码：17-21
• 全文大小：800 K

文摘

Congenital dyserythropoietic anemia type II, a recessive disorder of erythroid differentiation, is due to mutations in SEC23B, a component of the core trafficking machinery COPII. In no case homozygosity or compound heterozygosity for nonsense mutation(s) was found. This study represents the first description of molecular mechanisms underlying SEC23B hypomorphic genotypes by the analysis of five novel mutations. Our findings suggest that reduction of SEC23B gene expression is not associated with CDA II severe clinical presentation; conversely, the combination of a hypomorphic allele with one functionally altered results in more severe phenotypes. We propose a mechanism of compensation SEC23A-mediated which justifies these observations.