10个中国汉族寻常型鱼鳞病家系的FLG基因突变分析

目的 对10个寻常型鱼鳞病(ichthyosis vulgaris,Ⅳ)家系的FLG基因进行突变检测,并分析中国汉族人Ⅳ患者FLG基因的突变热点.方法 用聚合酶链反应扩增10个Ⅳ家系的所有患者及正常成员FLG基因的全部外显子,对扩增产物直接进行DNA测序检测突变,同时选取100名无亲缘关系的正常人作为对照.结果 在7个家系中发现了3种FLG基因的致病突变,包括c.3321delA、c.5757delCCAG和c.8138C＞T(p.S2706X),其中有两例患者的突变类型为3321delA的纯合突变,在另外3个家系中未发现FLG基因的突变.所有家系的正常成员和100名正常对照均未发现c.5757delCCAG和c.8138C＞T(p.S2706X),而在2名正常对照中发现其携带c.3321delA杂合突变.结论 在中国汉族Ⅳ家系检测到3种FLG基因的突变类型,其中c.3321delA是最常见的突变类型(46.9％).首次发现c.5757delCCAG和c.8138C＞T(p.S2706X)突变与Ⅳ相关.部分家系未检测到FLG基因突变,推测可能由其他致病基因导致.     

一例火棉胶样婴儿 TGM1基因变异的致病性研究

目的:探讨1个先天性常染色体隐性遗传性鱼鳞病家系的遗传学病因。方法:对1例火棉胶样婴儿进行全外显子组测序,Sanger测序验证基因变异位点。应用PolyPhen-2、PROVEAN和Mutation Taster软件以及蛋白同源建模方法预测基因变异的性质;实时荧光定量PCR和Western印迹法分析变异对等位基因mRN...     

Exacerbation of X-linked ichthyosis phenotype in a female by inheritance of filaggrin and steroid sulfatase mutations

Background

X-linked ichthyosis (XLI) is a relatively common, recessive condition caused by mutations in the steroid sulfatase (STS) gene. Common loss-of-function mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris and predispose individuals to atopic eczema.

Objective

To test the hypothesis that co-inheritance of FLG mutations can act as a genetic modifier in XLI.

Methods

An unusually severe XLI phenotype in addition to eczema and mild childhood asthma was investigated in a female Indian patient by fluorescent in situ hybridization (FISH) for the common STS gene deletion. Direct sequencing of the entire FLG gene was also performed.

Results

FISH analysis revealed that the proband was homozygous for the common STS genomic deletion mutation. Further investigation revealed a frame-shift mutation 3672del4 in the gene encoding filaggrin (FLG), leading to premature termination of profilaggrin translation. Interestingly, her father, who had a very typical mild presentation of XLI, did not carry this FLG mutation in addition to his STS deletion. Her mother was a heterozygous carrier of the FLG mutation and consistent with this, had mild symptoms of ichthyosis vulgaris; she was also a heterozygous carrier of the STS deletion.

Conclusion

This is the second reported case of the modifying effects of FLG null alleles on XLI and strengthens the hypothesis that filaggrin defects can synergize with STS deficiency to exacerbate the ichthyosis phenotype.