反常性痤疮致病基因定位研究
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摘要
反常性痤疮,又名化脓性汗腺炎,是一种慢性炎症性皮肤病,以反复发生的窦道及脓肿为主要特点。同时伴有聚合性痤疮、穿掘性脓肿性头部毛囊周围炎时称为毛囊闭塞三联征。
该病的病因和发病机制尚不明确。目前认为是由于毛囊漏斗部的上皮细胞过度增生造成毛囊口及皮脂腺的阻塞,皮脂排出不畅,继发细菌感染引起。遗传因素是最主要的病因,而内分泌及环境等因素影响基因表达。OMIM将其列为遗传性皮肤病(编号%142690)。目前报道的致病基因座有3个,分别位于1,6,19号染色体,但致病基因尚未明确。
收集到的两个家系来自河北省和河南省,均符合常染色体显性遗传。利用家系A进行全基因组扫描对致病基因进行初步定位,鉴定基因座位于19号染色体长臂。利用家系B进一步将该基因座精细定位于D19S416与D19S200之间5.0cM的范围,位于19q13.1-13.2。在连锁区域内的218个基因中,选择其中23个候选基因,对其外显子及剪接区域进行扩增和测序比对,但未发现致病突变。
本研究鉴定了反常性痤疮一个新的基因座,为致病基因鉴定打下了基础,从而为理解该病的分子发生机制、实现基因诊断和治疗创新提供了可能。
Acne inversa (Hidradenitis Suppurutiva, HS) is a chronic relapsing inflammatory skin disease characterized by recurrent draining sinuses and abscesses.
Current theories for its pathogenesis implicate hyperkeratosis of the follicular epithelium. Its aetiology is still poorly understood, dominantly associated with an initial genetic factor. The pattern of transmission is consistent with autosomal dominant inheritance (OMIM %142690) . At present, 3 loci for this disorder were reported and localized to chromosome 1,6, 19, but no gene responsible for it.
Two four-generation families from China with HS features were recruited. We undertook an entire genome-wide scan in pedigree A and and identified responsible locus at chromosome 19q. We confirmed the locus by pedigree B and further refined the locus at 19q13.1-13.2 and identified that one gene responsible for HS lies in the 5.0cM interval between D19S416 and D19S200.
There are about 218 genes within the 7.4Mb critical regions. We selected 23 relatively-known genes as candidates. The exons and splicing region of these genes were sequenced with no significant mutation.
This study will aid future identification of the responsible gene, which will be useful for understanding of the molecular mechanism of HS, implementing gene diagnosis and bringing new ideas for treatment as well as the pathogenesis of the pilosebaceous unit disorders.
该病的病因和发病机制尚不明确。目前认为是由于毛囊漏斗部的上皮细胞过度增生造成毛囊口及皮脂腺的阻塞,皮脂排出不畅,继发细菌感染引起。遗传因素是最主要的病因,而内分泌及环境等因素影响基因表达。OMIM将其列为遗传性皮肤病(编号%142690)。目前报道的致病基因座有3个,分别位于1,6,19号染色体,但致病基因尚未明确。
收集到的两个家系来自河北省和河南省,均符合常染色体显性遗传。利用家系A进行全基因组扫描对致病基因进行初步定位,鉴定基因座位于19号染色体长臂。利用家系B进一步将该基因座精细定位于D19S416与D19S200之间5.0cM的范围,位于19q13.1-13.2。在连锁区域内的218个基因中,选择其中23个候选基因,对其外显子及剪接区域进行扩增和测序比对,但未发现致病突变。
本研究鉴定了反常性痤疮一个新的基因座,为致病基因鉴定打下了基础,从而为理解该病的分子发生机制、实现基因诊断和治疗创新提供了可能。
Acne inversa (Hidradenitis Suppurutiva, HS) is a chronic relapsing inflammatory skin disease characterized by recurrent draining sinuses and abscesses.
Current theories for its pathogenesis implicate hyperkeratosis of the follicular epithelium. Its aetiology is still poorly understood, dominantly associated with an initial genetic factor. The pattern of transmission is consistent with autosomal dominant inheritance (OMIM %142690) . At present, 3 loci for this disorder were reported and localized to chromosome 1,6, 19, but no gene responsible for it.
Two four-generation families from China with HS features were recruited. We undertook an entire genome-wide scan in pedigree A and and identified responsible locus at chromosome 19q. We confirmed the locus by pedigree B and further refined the locus at 19q13.1-13.2 and identified that one gene responsible for HS lies in the 5.0cM interval between D19S416 and D19S200.
There are about 218 genes within the 7.4Mb critical regions. We selected 23 relatively-known genes as candidates. The exons and splicing region of these genes were sequenced with no significant mutation.
This study will aid future identification of the responsible gene, which will be useful for understanding of the molecular mechanism of HS, implementing gene diagnosis and bringing new ideas for treatment as well as the pathogenesis of the pilosebaceous unit disorders.
引文
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[5] Attanoos RL, Appleton MA, Douglas-Jones AG. The Pathogenesis of hidradenitis suppurativa: a closer look at apocrine and apoeccrine glands.[J].Brit. J. Dermtol.1995; 133:254-258.
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