一念珠状发家系Ⅱ型毛发角蛋白基因检测

Detection of Type ⅡHair Keratin Gene in a Family with Monilethrix

目的检测一念珠状发家系Ⅱ型毛发角蛋白(hHB)基因的突变情况。方法在取得遗传学研究知情同意书后,采集先证者及其家系成员外周血并提取基因组DNA。运用聚合酶链式反应(PCR)扩增hHB1和hHB6所有外显子,进行DNA直接测序,然后与GenBank中登记序列进行比对分析。结果该家系患者未发现已报道的10种hHB致病突变,但发现该家系hHB1基因外显子1第154位存在(G/C)杂合峰,以C为主,编码氨基酸为CGA(精氨酸R));与该家系无关的50人份测序为同样(G/C)杂合峰,但以G为主,而GeneBank中氨基酸编码为GGA(甘氨酸G),证实为非同义cSNPs(第154位G/C,G52R)。结论该家系念珠状发患者的致病基因不同于现已报道的10种hHB致病突变,在他们hHB1外显子1存在非同义cSNPs。

Objective To investigate the mutation of type Ⅱhuman basic hair keratin （hHb/ KRTHB） gene in a family of monilethrix. Methods Informed consent for the study was obtained from the proband and his family members. Their peripheral blood samples were extrcated from their genomic DNA. All exons of hHb1 and hHb6 were amplified by polymerase chain reaction （PCR）. All PCR products were sequenced directly using ABI3730 automated sequencer. These sequences were compared with those in GenBank with BLAST software. Results A series of specific PCR products were obtained from all specimens. The 10 missense mutations in hHb which had been reported were not identified in our study pedigree. A G/C heteropaek （154th）, predominant C, was identified in exon 1 of hHb1 gene from this family members, which encoded Arginine （52th）. An identical sequencing graph, predomiant G, was identifiend in 50 unrelated normal members, it was GGA（coding Glycine） in GeneBank. It showed that this change was a nonsynonymous cSNPs （154th G/C, G52R）. Conclusion There is a pathogenic gene in our study family, which is different from the 10 reported pathogenic mutations in hHb gene. There is a nonsynonymous cSNPs identified in the exon 1 of hHb1 gene in this family.