Spectrum of ELANE mutations in congenital neutropenia: a single-centre study in patients of Indian origin
Spectrum of ELANE mutations in congenital neutropenia: a single-centre study in patients of Indian origin
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DOI：
10.1136/jclinpath-2018-205235
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发表时间：
2018-12-01
影响因子：
3.4
通讯作者：
Balasubramanian, Poonkuzhali
中科院分区：
文献类型：
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作者：
Arun, A. Kumar;Senthamizhselvi, Anandan;Balasubramanian, Poonkuzhali
先天性和周期性中性粒细胞减少症是一种罕见的遗传性疾病，由于缺乏成熟的中性粒细胞，导致反复发生危及生命的细菌感染。周期性中性粒细胞减少症通常由杂合ELANE突变引起，而先天性中性粒细胞减少症在基因如ELANE、HAX-1、G6 PC 3和GFI 1中具有遗传异质性。ELANE突变的存在有助于诊断的建立，并排除中性粒细胞减少症的其他次要原因，如自身免疫性血细胞减少症和发展性再生障碍。此外，具有ELANE突变的患者也处于发生骨髓增生异常或急性髓性白血病的高风险中。因此，重要的是要筛选这些突变的患者出现中性粒细胞减少症的早期life.Methods这项研究包括52例患者进行了评估遗传性中性粒细胞减少症。结果11例患者ELANE基因存在10种不同的错义、移码或剪接位点变异：c. 125C>T（p.Pro42Leu），c. 164G>A（p.Cys55Tyr），c. 169G>A（p.Ala57Thr），c. 179T>C（p.Ile60Thr），c. 770C>T（p.Pro257Leu），c. 367-8C>A，c. 597+1G>A沿着三个新突变c. 302T>A（p.Val101Glu），c. 468G>T（p.Try156Cys）和c. 596delT（Phe199Ser fs* 13）。3例患者的家系研究，在所有的三种情况下，突变有一个从头origin.Conclusion突变的广泛分布表明，需要筛选所有的外显子在ELANE基因的基因型的适当表征。
Aims Congenital and cyclical neutropenia are rare inherited diseases that result in recurrent life-threatening bacterial infections due to a deficiency of mature neutrophils. Cyclical neutropenia is usually caused by heterozygous ELANE mutations while congenital neutropenia is genetically heterogeneous with mutations in genes like ELANE, HAX-1, G6PC3 and GFI1. The presence of ELANE mutation aids in the establishment of diagnosis and rules out other secondary causes of neutropenia such as autoimmune cytopenia and evolving aplasia. Further, patients with ELANE mutations are also at a high risk of developing myelodysplasia or acute myeloid leukaemia. Hence it is important to screen for these mutations in patients presenting with neutropenia early in life.Methods The study included 52 patients who were evaluated for inherited neutropenia. Genomic DNA was extracted from peripheral blood leucocytes and mutation analysis was done by bidirectional Sanger sequencing.Results Ten different missense, frameshift or splice site variants in ELANE gene were identified in 11 patients: c. 125C>T (p.Pro42Leu), c. 164G>A (p.Cys55Tyr), c. 169G>A (p.Ala57Thr), c. 179T>C (p.Ile60Thr), c. 770C>T (p.Pro257Leu), c. 367-8C>A, c. 597+1G>A along with three novel mutations c. 302T>A (p.Val101Glu), c. 468G>T (p.Try156Cys) and c. 596delT (Phe199Ser fs* 13). Family studies were available for three patients and, in all three instances, the mutation had a de novo origin.Conclusion The widespread distribution of mutations suggests the need to screen all the exons in ELANE gene for proper characterisation of the genotype.