女性Wiskott-Aldrich综合征一例及其研究进展-现代医学

女性Wiskott-Aldrich综合征一例及其研究进展

单位：南京医科大学附属儿童医院血液肿瘤科, 江苏南京 210008

分类号：R725.9

出版年·卷·期（页码）：2024·52·第一期（143-148）

摘要：

Wiskott-Aldrich综合征(WAS)是一种以血小板减少、湿疹和免疫缺陷为特征的X-连锁隐形遗传病，主要由编码WAS蛋白(WASp)的基因突变所致。发病多见于男性，国内外罕有女性患者报道。本文作者报道南京市儿童医院确诊的1例女性WAS。病初患儿因“面色苍白2个月，发现皮肤出血点2 d”入院，病程6年余，伴湿疹、反复感染、自身免疫性贫血、血小板减少。基因分析发现患儿WAS基因1号外显子上携带来源于母亲的杂合无义突变，但因表达正常WAS基因的X染色体发生失活偏移，导致女性患病。本文作者回顾该例患者的临床特征，结合遗传分析并检索国内外相关文献，总结女性WAS的发病模式，旨在呼吁临床医师高度重视女性WAS，及时甄别疑似患者行遗传咨询，提高早期诊断、减少误诊。

Wiskott-Aldrich syndrome(WAS) is a rare X-linked recessive genetic disease characterized by thrombocytopenia, eczema, and immunodeficiency, which is mainly caused by abnormal expression of Wiskott-Aldrich syndrome protein(WASp) due to WAS genemutation. WAS is mainly reported in males, few in females. Here we reported a female case who was diagnosed with WAS in Nanjing Children's Hospital. The girl was hospitalized due to pale complexion for 2 months and petechiae for 2 days. The main clinical manifestations were autoimmune amentia, thrombocytopenia accompanied with eczema, recurrent infections for 6 years. Genetic analysis revealed the girl carried a heterozygous nonsense mutation existed in exon 1 of WAS gene, from her mother. Furthermore, the X-chromosomes bearing normal WAS gene werepredominantly inactivated, which might elucidate the pathogenesis of WAS in females. Hence, we summarized clinical manifestation and genetic analysis, with literature review in female WAS. We hope to increase clinicians’ awareness of female patients. For those who are suspected of WAS, it is recommended to conduct a genetic analysis to diagnose and treat in time.

参考文献：

[1] OCHS H D,FILIPOVICH A H,VEYS P,et al.Wiskott-Aldrich syndrome:diagnosis,clinical and laboratory manifestations,and treatment[J].Biol Blood Marrow Transplant,2009,15(1 Suppl):84-90.
[2] COTELINGAM J D,WITEBSKY F G,HSU S M,et al.Malignant lymphoma in patients with the Wiskott-Aldrich syndrome[J].Cancer Investigation,1985,3(6):515-522.
[3] ARIGA T.Wiskott-Aldrich syndrome：an X-linked primary immunodeficiency disease with unique and characteristic features[J].Allergology International,2012,61(2):183-189.
[4] KWAN S P,LEHNER T,HAGEMANN T,et al.Localization of the gene for the Wiskott-Aldrich syndrome between two flanking markers,TIMP and DXS255,on Xp11.22-Xp11.3[J].Genomics,1991,10(1):29-33.
[5] HOU X,SUN J,LIU C,et al.Case report:Wiskott-Aldrich syndrome caused by extremely skewed X-chromosome inactivation in a Chinese girl[J].Frontiers in Pediatrics,2021,9:691524.
[6] MASSAAD M J,RAMESH N,GEHA R S.Wiskott-Aldrich syndrome:a comprehensive review[J].Annals of the New York Academy of Sciences,2013,1285:26-43.
[7] PAROLINI O,BERARDELLI S,RIEDL E,et al.Expression of Wiskott-Aldrich syndrome protein(WASP) gene during hematopoietic differentiation[J].Blood,1997,90(1):70-75.
[8] THRASHER A J,BURNS S O.WASP:a key immunological multitasker[J].Nature Reviews Immunology,2010,10(3):182-192.
[9] BLUNDELL M P,WORTH A,BOUMA G,et al.The Wiskott-Aldrich syndrome:the actin cytoskeleton and immune cell function[J].Disease Markers,2010,29(3-4):157-175.
[10] SUDHAKAR M,RIKHI R,LOGANATHAN S K,et al.Autoimmunity in Wiskott-Aldrich syndrome:updated perspectives[J].The Application of Clinical Genetics,2021,14:363-388.
[11] AMARINTHNUKROWH P,ITTIPORN S,TONGKOBPETCH S,et al.Clinical and molecular characterization of Thai patients with Wiskott-Aldrich syndrome[J].Scandinavian Journal of Immunology,2013,77(1):69-74.
[12] PATRAT C,OUIMETTE J F,ROUGEULLE C.X chromosome inactivation in human development[J].Development(Cambridge,England),2020,147(1):dev183095.
[13] HARPER P S.Mary Lyon and the hypothesis of random X chromosome inactivation[J].Human Genetics,2011,130(2):169-174.
[14] UCHIDA T,OHASHI H,AOKI E,et al.Clonality analysis by methylation-specific PCR for the human androgen-receptor gene(HUMARA-MSP)[J].Leukemia,2000,14(1):207-212.
[15] ALLEN R C,ZOGHBI H Y,MOSELEY A B,et al.Methylation of HpaⅡ and HhaⅠ sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X-chromosome inactivation[J].American Journal of Human Genetics,1992,51(6):1229-1239.
[16] TAKIMOTO T,TAKADA H,ISHIMURA M,et al.Wiskott-Aldrich syndrome in a girl caused by heterozygous WASP mutation and extremely skewed X-chromosome inactivation:a novel association with maternal uniparental isodisomy 6[J].Neonatology,2015,107(3):185-90.
[17] LUTSKIY M I,SASAHARA Y,KENNEY D M,et al.Wiskott-Aldrich syndrome in a female[J].Blood,2002,100(8):2763-2768.
[18] ANDREU N,PUJOL-MOIX N,MARTINEZ-LOSTAO L,et al.Wiskott-Aldrich syndrome in a female with skewed X-chromosome inactivation[J].Blood Cells,Molecules & Diseases,2003,31(3):332-337.
[19] LIU D W,ZHANG Z Y,ZHAO Q,et al.Wiskott-Aldrich syndrome/X-linked thrombocytopenia in China:clinical characteristic and genotype-phenotype correlation[J].Pediatric Blood & Cancer,2015,62(9):1601-1608.
[20] BURROUGHS L M,PETROVIC A,BRAZAUSKAS R,et al.Excellent outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome:a PIDTC report[J].Blood,2020,135(23):2094-2105.
[21] ALBERT M H,SLATTER M A,GENNERY A R,et al.Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome:an EBMT inborn errors working party analysis[J].Blood,2022,139(13):2066-2079.
[22] CAVAZZANA M,THRASHER A.Gene therapy for Whiskott-Aldrich syndrome:the latest news[J].Clinical and Translational Medicine,2022,12(4):e815.
[23] FERRUA F,MARANGONI F,AIUTI A,et al.Gene therapy for Wiskott-Aldrich syndrome:history,new vectors,future directions[J].The Journal of Allergy and Clinical Immunology,2020,146(2):262-265.
[24] SULLIVAN K E,MULLEN C A,BLAESE R M,et al.A multiinstitutional survey of the Wiskott-Aldrich syndrome[J].The Journal of Pediatrics,1994,125(6 Pt 1):876-885.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录