常染色体隐性遗传性鱼鳞病一家系表型、基因型与皮损超微结构研究

Phenotype, genotype and ultrastructural findings in a pedigree with autosomal recessive congenital ichthyosis

目的 探讨常染色体隐性遗传性鱼鳞病家系临床表型、基因型及超微结构.方法 观察常染色体隐性遗传性鱼鳞病患者临床表现.用PCR扩增TGM1基因15个外显子及其邻近剪切位点,双向直接测序;取先证者背部皮损做透射电镜观察,记录电镜表现特征.结果 先证者临床表现介于板层状鱼鳞病及非大疱性鱼鳞病样红皮病之间,其弟弟为火棉胶婴儿.先证者、其弟及父亲3号外显子第551位碱基胞嘧啶（C）→胸腺嘧啶（T）,其编码的第143位氨基酸由精氨酸变为半胱氨酸（R143C）;先证者、其弟及母亲4号外显子第759位胞嘧啶（C）→胸腺嘧啶（T）,使第212位氨基酸由丝氨酸转变为苯丙氨酸（S212F）.电镜观察发现,先证者皮损不仅有Ⅱ型结构表现,也同时存在Ⅲ型结构特征.结论 该家系患者携带复合杂合突变,R143C属于热点区,S212F为新发现的位点.携带TGM1基因突变的先证者皮损电镜表现为Ⅱ型,但同时发现有Ⅲ型结构存在.

Objective To investigate the clinical phenotype, genotype and ultrastructural features in a pedigree with autosomal recessive congenital ichthyosis. Methods Patients were examined for clinical manifestation. PCR was carried out to amplify all the 15 exons and adjacent splice sites of TGM1 gene followed by bidirectional sequencing. Skin samples were taken by biopsy from the back of the proband, fixed in 3% glu-taraldehyde for transmission electron microscopy. Results The proband presented an intermediate clinical phenotype between lamellar ichthyosis （LI） and non-bullous congenital ichthyosiform erythroderma （NCIE）, while his brother manifested as a collodion baby. A C551T heterozygous mutation which located in the third exon of TGM1 gene and resulted in a substitution of arginine by cysteine at codon 143 （R143C）, was detected in the proband, his brother and father. Meanwhile, another heterozygous C-to-T transition at position 759 causing a substitution of serine by phenylalanine at codon 212 （S212F）, was noted in the proband, his brother and mother. Electron microscopy revealed not only features of ichthyosis congenital type Ⅲ but also those of ichthyosis congenital type Ⅱ in lesions of the proband. Conclusions The patients in this pedigree carry compound heterozygous mutations, i.e. R143C, a hot missense mutation, as well as a de novo mutation S212F. The proband, who harbors mutations in the TGM1 gene, shows electron microscopic features characteristic not only of ichthyosis congenital type Ⅱ but also of ichthyosis congenital type Ⅲ.