Prenatal diagnosis of epidermolytic hyperkeratosis by direct gene sequencing.
Prenatal diagnosis of epidermolytic hyperkeratosis by direct gene sequencing.
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通过直接基因测序对表皮松解性角化过度进行产前诊断。
DOI：
10.1111/1523-1747.ep12371723
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Roop,DR
中科院分区：
文献类型：
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作者：
Rothnagel,JA;Longley,MA;Holder,RA;Küster,W;Roop,DR
表皮松解性角化过度症（大疱性先天性鱼鳞病型红皮病）是一种由基底上角蛋白缺陷引起的常染色体显性皮肤病。最近，角蛋白1和10的突变已被确定在这种疾病的患者。在这项研究中，直接基因测序被用来建立产前诊断15周妊娠双胞胎的风险表皮增生性角化症。从受影响的父亲和绒毛样本的基因组DNA的直接序列分析显示，酪氨酸天冬酰胺突变的高度保守的角蛋白10的1A α-螺旋段内的位置14。未受影响的家庭成员进行了分析，表现出这种突变，也没有多态性变异在正常人群中观察到在这个位置。该残基在迄今为止测序的所有I型角蛋白中是不变的，并且在相关的中间丝蛋白如波形蛋白和核纤层蛋白中也是保守的。鉴于这种高度的保守性，该位置的任何突变都可能是有害的，并将导致疾病。
Epidermolytic hyperkeratosis (bullous congenital ichthyosi-form erythroderma) is an autosomal dominant skin disorder caused by defects in the suprabasal keratins. Recently, mutations in the keratins 1 and 10 have been identified in patients with this disease. In this study, direct gene sequencing was used to establish the prenatal diagnosis in 15-week gestation twins at risk for epidermolytic hyperkeratosis. Direct sequence analysis of genomic DNA from the affected father and from both chorionic villus samples revealed a tyrosine to asparagine mutation at position 14 within the highly conserved 1A alpha-helical segment of keratin 10. None of the unaffected family members that were analyzed exhibit this mutation nor have polymorphic variations been observed in the normal population at this position. This residue is invariant in all type I keratins sequenced to date and is also conserved in related intermediate filament proteins such as vimentin and lamin. Given this high degree of conservation it is probable that any mutation at this position is deleterious and will result in disease.