体细胞嵌合父亲传递致女性杜氏肌营养不良一例家系及遗传学分析  

Family genetic analysis of paternal Dystrophin gene mutations in a case of female Duchenne muscular dystrophy

作　　者：毛莹莹[1] 陈倩[1] 张学 许克铭[1] 高志杰[1] 张平平 Mao Yingying;Chen Qian;Zhang Xue;Xu Keming;Gao Zhijie;Zhang Pingping(Department of Neurology,Children′s Hospital of Capital Institute of Pediatrics,Beijing 100020,China;Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]首都儿科研究所附属儿童医院神经内科,北京100020 [2]中国医学科学院基础研究所遗传学系,北京100730

出　　处：《中华医学杂志》2021年第48期3973-3976,共4页National Medical Journal of China

基　　金：国家重点研发计划(2016YFC0905101);中国医学科学院医学与健康科技创新工程(2016-I2M-1-002)。

摘　　要：报道1例父源嵌合体遗传的女性杜氏肌营养不良(DMD)家系及遗传学分析,先证者DMD基因未发现大片段缺失/重复,二代测序结果显示先证者存在DMD基因(NM_004006)c.4707C>A(p.C1569X)杂合突变,致病性分析为致病性突变。Sanger测序显示先证者父亲携带同一位点突变,父亲嵌合比例约为17.7%。特异性酶切检测显示先证者存在母源性X染色失活偏倚。X染色体隐性遗传病DMD可发生于女性,极少数可为父源遗传。女性患者需高度关注X染色体失活偏倚,可疑新生突变患者,不除外嵌合体携带,尤其是表型正常的父系嵌合体遗传,再生育需进行产前基因筛查。A pedigree genetic analysis of a female Duchenne muscular dystrophy(DMD)inherited from paternal chimerism was conducted to explore the genetic diagnosis strategy.No large deletions/duplications was found in the DMD gene of the proband.Next-generation sequencing(NGS)results showed that the proband had a heterozygous mutation in the DMD gene c.4707C>A(p.C1569X).This locus has not been reported in the literature and is considered as a pathogenic mutation.Sanger sequencing revealed that the father of the proband carried the same mutation,and the mosaic ratio was about 17.7%.The specific enzyme digestion test showed that the proband had maternal skewed X-inactivation.DMD a recessive inherited disease of the X chromosome,exists in female patients,and very few of them are inherited from paternal origin.Female patients need to pay close attention to skewed X-inactivation and suspected new mutations.Mosaic is not excluded,especially the inheritance of paternal mosaicism with normal phenotype.Prenatal gene screening is necessary for reproduction.

关 键 词：肌营养不良 杜氏 基因 父源 X染色体失活偏倚 

分 类 号：R725.9[医药卫生—儿科]