2例围生期型常染色体隐性多囊肾病家系的PKHD1基因变异分析

    PKHD1 gene mutation analysis in two families of perinatal stage autosomal recessive polycystic kidney disease

      摘要
    • 摘要:
      目的  对2例常染色体隐性多囊肾病（autosomal recessive polycystic kidney disease，ARPKD）家系进行基因变异分析，明确致病原因，为ARPKD的早期诊断、治疗、遗传咨询及产前诊断提供理论依据。
      方法  收集2例胎儿引产组织及父母外周血进行全外显子测序分析，结合Sanger测序进行家系分析及位点验证。
      结果  全外显子组测序及Sanger测序提示家系1胎儿PKHD1基因存在c.3436C＞T（p.Q1146X）和c.1981A＞C（p.T661P）复合杂合变异；家系2曾生育1例ARPKD患儿，1岁时死于心力衰竭，本例胎儿PKHD1基因存在c.9719G＞A（p.R3240Q），c.10057C＞T（p.L3353F）和c.7237C＞T（p.R2413C）复合杂合变异。
      结论  两个家系均为PKHD1基因变异导致的围生期型ARPKD，共发现5个基因变异位点，其中2个为新发变异位点，c.10057C＞T和c.1981A＞C均为错义变异。鉴于ARPKD基因型和表型的复杂性，及早进行家系的遗传咨询将有助于基因诊断和早期产前诊断。

       

      Abstract:
      Objective  To analyze genetic variation in two cases of autosomal recessive polycystic kidney disease （ARPKD） and provide theoretical rationales for its early diagnosis, treatment, genetic counseling and prenatal diagnosis.
      Methods  Fetal tissues and parental peripheral blood samples of two children were collected for whole exon sequencing, pedigree analysis and site verification.
      Results  Whole exome and Sanger sequencing revealed compound heterozygous mutations in c.3436C＞T （p.Q1146X） and c.1981A＞C （p.T661P） in fetal PKHD1 gene in family 1. And one ARPKD child of family 2 previously died of heart failure at the age of 1 year. In this case, c.9719G＞A （p.R3240Q）, c.10057C＞T （p.L3353F） and c.7237C＞T （p.R2413C） compound heterozygous mutations were detected in fetal PKHD1 gene.
      Conclusion  Both families had perinatal stage ARPKD caused by variants in PKHD1 gene and 5 genetic variant loci, including 2 new missense variants of c.10057C＞T and c.1981A＞C. In light of a great complexity of ARPKD genotype and phenotype, early genetic counselling of the pedigree may facilitate genetic diagnosis and early prenatal diagnosis.

       

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