Gao Ying, Bai Jin-li, Liu Xiao-yan, Qu Yu-jin, Cao Yan-yan, Wang Jian-cai, Jin Yu-wei, Wang Hong, Song Fang
Capital Institute of Pediatrics, Beijing 100020, China.
J Zhejiang Univ Sci B. 2015 Nov;16(11):957-62. doi: 10.1631/jzus.B1500080.
Kindler syndrome (KS; OMIM 173650) is a rare autosomal recessive skin disorder, which results in symptoms including blistering, epidermal atrophy, increased risk of cancer, and poor wound healing. The majority of mutations of the disease-determining gene (FERMT1 gene) are single nucleotide substitutions, including missense mutations, nonsense mutations, etc. Large deletion mutations are seldom reported. To determine the mutation in the FERMT1 gene associated with a 7-year-old Chinese patient who presented clinical manifestation of KS, we performed direct sequencing of all the exons of FERMT1 gene. For the exons 2-6 without amplicons, we analyzed the copy numbers using quantitative real-time polymerase chain reaction (qRT-PCR) with specific primers. The deletion breakpoints were sublocalized and the range of deletion was confirmed by PCR and direct sequencing. In this study, we identified a new 17-kb deletion mutation spanning the introns 1-6 of FERMT1 gene in a Chinese patient with severe KS phenotypes. Her parents were carriers of the same mutation. Our study reported a newly identified large deletion mutation of FERMT1 gene involved in KS, which further enriched the mutation spectrum of the FERMT1 gene.
Kindler综合征(KS;OMIM 173650)是一种罕见的常染色体隐性遗传性皮肤病,其症状包括水疱形成、表皮萎缩、癌症风险增加以及伤口愈合不良。致病基因(FERMT1基因)的大多数突变是单核苷酸替换,包括错义突变、无义突变等。大的缺失突变很少被报道。为了确定与一名出现KS临床表现的7岁中国患者相关的FERMT1基因突变,我们对FERMT1基因的所有外显子进行了直接测序。对于没有扩增子的外显子2-6,我们使用特异性引物通过定量实时聚合酶链反应(qRT-PCR)分析拷贝数。通过PCR和直接测序对缺失断点进行亚定位并确认缺失范围。在本研究中,我们在一名具有严重KS表型的中国患者中鉴定出一种新的17kb缺失突变,该突变跨越FERMT1基因的内含子1-6。她的父母是相同突变的携带者。我们的研究报道了一个新发现的与KS相关的FERMT1基因大缺失突变,这进一步丰富了FERMT1基因的突变谱。