全外显子测序诊断不典型Netherton综合征伴水疱

Diagnosis of an atypical Netherton's syndrome with blister using whole exome sequencing

报告1例Netherton综合征(NS)。患儿女,14岁。出生后即无诱因进行性头颈、躯干红斑、水疱,环形双边状红斑鳞屑,反复发作14年伴全身干燥。全外显子高通量测序SPINK5基因染色体chr5:147470777发生c.652C>T(E8)截断性杂合突变,氨基酸改变p.218,R>X(877),其无义突变可能会导致蛋白翻译提前终止和染色体chr5:147503528位点发生IVS27+5G>A剪切位点杂合突变,其mRNA剪接可能会受影响。皮损组织病理改变类似银屑病样表现。免疫组化法检测LEKTI蛋白的表达与正常对照无显著差异。扫描电镜下未见特异性结节性(套叠性)脆发。患儿COL17A1、ITGB4、PLEC、CDSN、KRT1、KRT10、KRT2及DSG1基因均未见致病性突变。通过一代基因检测验证该患儿诊断为NS,基因检测是不典型NS的主要诊断方法。

A 14-year-old Han female with Netherton’s syndrome is reported. There were erythemas and blisters on the head, neck and torso, double ring-shaped erythemas with scales and dry skin since birth. High-throughput sequencing of all coding exons of SPINK5 genes showed truncating mutation on chromosome chr5:147470777 c.652 C>T(E8) replaced by p.218,R>X(877). This nonsense mutation may lead to early termination of protein translation and heterozygous mutations on chromosome chr5:147503528 locus IVS27+5 G>A, possibly affecting m RNA splicing. The pathological changes of skin lesions were similar to that of psoriasis. Immunohistochemistry showed no differences in expression of LEKTI protein between patient and normal control. No specific fragile nodular hair-shaft deformities were observed under scanning electron microscope. No pathogenic mutation was found in COL17 A1, ITGB4, PLEC, CDSN, KRT1, KRT10, KRT2 and DSG1 genes. The patient was diagnosed with Netherton’s syndrome by a generation of gene tests. Genetic examination is the main diagnostic method for atypical Netherton’s syndrome.