一例森森布伦纳综合征患儿的临床特点及基因突变分析

Clinical features and mutational analysis of a case with Sensenbrenner syndrome

目的探讨纤毛内转运系统（intraflagellar transport，IFT）43基因突变致森森布伦纳综合征（sensenbrenner syndrome）的临床特点及遗传学机制。方法提取患儿及父母外周血基因组DNA，利用液相捕获试剂盒将目标基因捕获出来，用新一代测序仪IlluminaHiSeq2500进行高通量测序并分析，找出可能致病突变基因，应用Sanger测序对患儿父母相关基因进行验证。结果患儿表现为身材矮小，四肢短，短指畸形、牙齿发育不全，网膜营养不良，慢性肾功能衰竭。基因测序结果显示患JLIFT43基因存在c．1A〉G（p．M1V）纯合突变，Sanger测序验证患儿父母均携带IFT43基因C．1A〉G（p．M1V）杂合变异。结论IFT43基因e．1A〉G（P．MIV）突变为该患儿的遗传学病因，为家系的遗传咨询和产前诊断提供了依据。

Objective To explore the clinical characteristics of a patient with Sensenbrenner syndrome （also called cranioectodermal dysplasia type 3） caused by mutation of intraflagellar transport （IFT） 43 gene. Methods The clinical data of the patient was retrospectively analyzed. The target genes was the patient were captured and subjected to next generation sequencing. Suspected mutations were verified through Sanger sequencing. Results The patient, a-13 year-and-5-month-old girl, was admitted for anemia and renal dysfunction for 8 months. Clinically, she has featured short stature, short limbs, brachydactylia, tooth agenesis, and retinal dystrophy, high-degree myopia, and chronic renal failure. Gene sequencing showed that she has carried a homozygous c. 1A^G （p. MIV） mutation of the IFT43 gene, for which both of her parents were heterozygous carriers. Conclusion c. 1A^G （p. M1V） mutation of the C140RF179/IFT43 gene is the cause for praecox chronic renal failure in children. Genetic testing can facilitate the diagnosis of this rare disorder. For affected families, prenatal diagnosis should be provided.