Genotype-phenotype correlations in hereditary elliptocytosis and hereditary pyropoikilocytosis

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• 作者：Omar Niss^a ; ^{omar.niss@cchmc.org" class="auth_mail" title="E-mail the corresponding author} ; Satheesh Chonat^b ; Neha Dagaonkar^c ; Marya O. Almansoori^d ; Karol Kerr^e ; Zora R. Rogers^f ; Patrick T. McGann^a ; Maa-Ohui Quarmyne^b ; Mary Risinger^g ; Kejian Zhang^c ; Theodosia A. Kalfa^a
• 关键词：HE ; hereditary elliptocytosis ; HPP ; hereditary pyropoikilocytosis ; RBC ; red blood cell ; Elmax ; the maximum value of elongation index
• 刊名：Blood Cells, Molecules and Diseases
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：61
• 期：Complete
• 页码：4-9
• 全文大小：996 K

文摘

Hereditary elliptocytosis (HE) and hereditary pyropoikilocytosis (HPP) are heterogeneous red blood cell (RBC) membrane disorders that result from mutations in the genes encoding α-spectrin (SPTA1), β-spectrin (SPTB), or protein 4.1R (EPB41). The resulting defects alter the horizontal cytoskeletal associations and affect RBC membrane stability and deformability causing shortened RBC survival. The clinical diagnosis of HE and HPP relies on identifying characteristic RBC morphology on peripheral blood smear and specific membrane biomechanical properties using osmotic gradient ektacytometry. However, this phenotypic diagnosis may not be readily available in patients requiring frequent transfusions, and does not predict disease course or severity. Using Next-Generation sequencing, we identified the causative genetic mutations in fifteen patients with clinically suspected HE or HPP and correlated the identified mutations with the clinical phenotype and ektacytometry profile. In addition to identifying three novel mutations, gene sequencing confirmed and, when the RBC morphology was not evaluable, identified the diagnosis. Moreover, genotypic differences justified the phenotypic differences within families with HE/HPP.