Gagne Katelyn E, Ghazvinian Roxanne, Yuan Daniel, Zon Rebecca L, Storm Kelsie, Mazur-Popinska Magdalena, Andolina Laura, Bubala Halina, Golebiowska Sydonia, Higman Meghan A, Kalwak Krzysztof, Kurre Peter, Matysiak Michal, Niewiadomska Edyta, Pels Salley, Petruzzi Mary Jane, Pobudejska-Pieniazek Aneta, Szczepanski Tomasz, Fleming Mark D, Gazda Hanna T, Agarwal Suneet
Division of Hematology/Oncology, Stem Cell Program, and.
Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA;
Blood. 2014 Jul 17;124(3):437-40. doi: 10.1182/blood-2014-01-545830. Epub 2014 Apr 15.
Pearson marrow pancreas syndrome (PS) is a multisystem disorder caused by mitochondrial DNA (mtDNA) deletions. Diamond-Blackfan anemia (DBA) is a congenital hypoproliferative anemia in which mutations in ribosomal protein genes and GATA1 have been implicated. Both syndromes share several features including early onset of severe anemia, variable nonhematologic manifestations, sporadic genetic occurrence, and occasional spontaneous hematologic improvement. Because of the overlapping features and relative rarity of PS, we hypothesized that some patients in whom the leading clinical diagnosis is DBA actually have PS. Here, we evaluated patient DNA samples submitted for DBA genetic studies and found that 8 (4.6%) of 173 genetically uncharacterized patients contained large mtDNA deletions. Only 2 (25%) of the patients had been diagnosed with PS on clinical grounds subsequent to sample submission. We conclude that PS can be overlooked, and that mtDNA deletion testing should be performed in the diagnostic evaluation of patients with congenital anemia.
皮尔逊骨髓胰腺综合征（PS）是一种由线粒体DNA（mtDNA）缺失引起的多系统疾病。钻石黑范贫血（DBA）是一种先天性低增殖性贫血，其中核糖体蛋白基因和GATA1的突变与之相关。这两种综合征有几个共同特征，包括严重贫血的早发、可变的非血液学表现、散发性遗传发生以及偶尔的自发血液学改善。由于PS的特征重叠且相对罕见，我们推测一些主要临床诊断为DBA的患者实际上患有PS。在这里，我们评估了提交用于DBA基因研究的患者DNA样本，发现173例基因未明确的患者中有8例（4.6%）含有大的mtDNA缺失。样本提交后，只有2例（25%）患者基于临床诊断为PS。我们得出结论，PS可能被忽视，并且在先天性贫血患者的诊断评估中应进行mtDNA缺失检测。
