title: [Mutation analysis of WASP gene and prenatal diagnosis of Wiskott-Aldrich syndrome].
abstract: OBJECTIVE
  Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, and an increased incidence of autoimmunity and malignancies. The patients always have a severe clinical phenotype that can result in death if not diagnosed and treated early in life. The treatment of choice with the best outcome is hematopoietic stem cell transplantation, preferably from a matched related donor. But uncertain treatment effect and high treatment cost limit its clinical application. It is the best strategy that avoiding birth of a fetus with defect through prenatal diagnosis at present. This study aimed to analyze the mutation of WASP gene in 4 Chinese families with WAS and to provide prenatal diagnosis for the high-risk fetus.
  
  
  METHODS
  The probands of the four WAS families were all males, one of whom was deceased but had a family history and clinical datas integrated. All the patients were detected with blood routine tests, immunological tests and bone marrow examination. PCR and bilateral direct sequencing of PCR product was carried out in the regions of exon and exon-intron boundaries of WASP gene for 3 probands, 4 mothers and 100 unrelated healthy individuals as control. Prenatal diagnosis was provided for the two fetuses at the first trimester by mutation analysis.
  
  
  RESULTS
  Four WASP gene mutations were detected: c.91A > G (p.E31K), c.665C > T (p.R211X), c.397G > A (p.E133K), c.952-953delCC (p. P317fsX18), among which c.952-953delCC (p. P317fsX18) was first reported. Mothers in Family 2, 3 and 4 were carriers of WASP gene mutation, but family 1 was considered as a de-novo mutation. None of the 100 unaffected subjects had the above mutants. Prenatal diagnosis indicated that the fetus in family 2 was male and carried the same mutation as the proband, so the fetus was presumably to be a patient. The parents decided to receive an induced abortion. Following the termination of the pregnancy, the result of gene analysis of the aborted tissues was consistent with prenatal diagnosis. The fetus in family 3 was normal male confirmed by normal test results six months after birth.
  
  
  CONCLUSIONS
  The 4 mutations of the WASP gene probably were causative to the families of WAS, among which c.952-953delCC was reported for the first time. Prenatal diagnosis by DNA sequencing is the effective method to avoid birth of WAS patient.
authors.affiliation: Prenatal Diagnosis Center,Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Huirong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Email: kongxd@263.net.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Kong
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Wu
authors.forename: Xueju
authors.initials: X
authors.lastname: Xu
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Bai
authors.forename: Yin
authors.initials: Y
authors.lastname: Feng
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis*; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis; D017422:Sequence Analysis, DNA; D014923:Wiskott-Aldrich Syndrome / Q000175:diagnosis* / Q000235:genetics; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics*; D053632:X-Linked Combined Immunodeficiency Diseases
chemical_list: D051316:Wiskott-Aldrich Syndrome Protein