Ancliff Phil J, Gale Rosemary E, Linch David C
department of Haematology, Geat Ormond Street Hospital , Great Ormond Street, London, UK.
Hematology. 2003 Jun;8(3):165-71. doi: 10.1080/1024533031000107497.
Severe congenital neutropenia (SCN) was originally described as an autosomal recessive disorder. Autosomal dominant and sporadic forms of the disease have subsequently been recognized. All forms of the disease are manifest by persistent severe neutropenia and recurrent bacterial infection. Cyclical neutropenia (CyN) is characterized by periodic neutropenia inter-spaced with (near) normal neutrophil counts. Recently, heterozygous mutations in the ELA2 gene encoding neutrophil elastase (NE) have been described in the majority of cases of CyN and sporadic and autosomal dominant SCN. A case of paternal mosaicism has provided genetic "proof" of the pathogenicity of such mutations, but the exact pathogenic mechanism remains elusive. This review will focus on the mosaic proof and examine possible pathogenic mechanisms. The lack of obvious associations and indeed overlap between the mutations that cause the two diseases will also be discussed. Clinically to date, the discovery of an elastase mutation has been of limited value to individual patients. However, it is hoped that further genotype/phenotype studies may improve assessment of patient prognosis.
严重先天性中性粒细胞减少症（SCN）最初被描述为常染色体隐性疾病。随后又认识到了该疾病的常染色体显性和散发形式。该疾病的所有形式均表现为持续性严重中性粒细胞减少和反复细菌感染。周期性中性粒细胞减少症（CyN）的特征是周期性中性粒细胞减少，其间伴有（接近）正常的中性粒细胞计数。最近，在大多数CyN以及散发和常染色体显性SCN病例中，均发现了编码中性粒细胞弹性蛋白酶（NE）的ELA2基因杂合突变。一例父系嵌合体为这类突变的致病性提供了遗传学“证据”，但其确切致病机制仍不清楚。本综述将聚焦于嵌合体证据，并探讨可能的致病机制。还将讨论导致这两种疾病的突变之间缺乏明显关联以及实际上的重叠情况。迄今为止，在临床上，弹性蛋白酶突变的发现对个体患者的价值有限。然而，希望进一步的基因型/表型研究可能会改善对患者预后的评估。
