利用全基因组连锁分析和外显子测序搜寻新的反常性痤疮致病基因

Acne inversa(AI) is a chronic inflammatory follicular disease, which have recurrent cutaneous abscess formation and severe scarring, seriously affecting the quality of life. It's genetic pathogenesis has been associated with the mutations of γ-secretase gene(PSENEN, PSEN1, NCSTN). But some reported that not all IA pedigrees have γ-secretase gene mutations. In recent years we carried out a preliminary STR linkage analysis in two pedigrees with AI, all two families had been excluded from the regions reported in multiple regions of Chromosome 1; 6; 14; 19, PCR sequencing did not identified the reported γ-secretase gene mutations (PSENEN, PSEN1, NCSTN). These results suggest that there may be new AI genes in our pedigrees. Based on this, we intend to use genome-wide linkage analysis and exon capture and high-throughput sequencing jointly to search the new candidate genes with bioinformatics analysis,to determine the new pathogenetic genes after verificating within these families, sporadic cases and normal controls, and take the preliminary analysis of gene function. This work might lay the foundation for further elucidating the pathogenesis of this disease.

反常性痤疮（AI）是一种毛囊慢性炎症性疾病，反复形成痛性皮肤脓肿及严重疤痕，严重影响患者生活质量。研究报道部分家系与γ-分泌素基因（PSENEN、PSEN1、NCSTN）突变有关，但有多项研究未能在所有家系中发现该基因的突变。我们在前期工作中也发现仅有部分家系存在γ-分泌素基因（PSENEN、PSEN1、NCSTN）突变，说明存在其它致病基因在AI发病中起作用。因此我们基于2个已排除已经报道连锁区域和已知致病基因突变的两个AI大家系，拟联合利用全基因组连锁分析和外显子捕获高通量测序方法, 对测序数据进行生物信息学分析筛选候选基因，在确定候选基因后进行家系内和散发病例验证，并与正常对照对候选基因进行验证，对致病基因功能进行初步验证，为进一步阐明本病的发病机制奠定基础。

反常性痤疮（AI）是毛囊的一种慢性炎症性疾病，严重影响患者生活质量。我们利用临床工作中收集的一个AI大家系，完成了该家系的外显子捕获高通量测序, 对测序数据进行生物信息学分析筛选出多个候选基因，并完成了家系内和散发病例的验证，确定了该家系的致病基因为并与正常对照进行验证，最后确定本家系的致病基因是NCSTN，突变位点在NCSTN的8号外显子944位C被T代替，导致的氨基酸突变为p. A315V，检索确定为新的基因和氨基酸突变位点，为进一步研究本病的发病机制打下基础。