背景:先天性鱼鳞病是一组不同的角质化疾病,与不同严重程度的大面积皮肤鳞屑相关。先天性鱼鳞病的非综合征形式进一步分为普通鱼鳞病(寻常型鱼鳞病和X连锁鱼鳞病),常染色体隐性先天性鱼鳞病,和角化病性鱼鳞病.
目的:鉴定涉及不同形式的遗传性鱼鳞病的序列变异。
方法:我们研究了八个不同类型鱼鳞病的家庭,包括四个常染色体隐性遗传先天性鱼鳞病的家庭和四个常见鱼鳞病的家庭。进行全外显子组测序和基于PCR的基因分型以找出疾病的分子基础。
结果:在一个家庭中,新的重复序列变体NM_002016.2:c.2767dupT;NP_002007.1:p.在FLG基因中鉴定出Ser923PhefsTer2;在四个家族中,先前报道的无义序列变体NM_000359.3:c.232C>T;NP_002007.1:p。在TGM1基因中鉴定出Arg78Ter,while,在X连锁隐性鱼鳞病的三个家族中,整个STS基因(NM_001320752.2;NP_001307681.2)区域被删除。
结论:尚未进行基因表达研究以加强计算分析的发现。
结论:这项研究强调了TGM1基因中c.232C>T变体作为可能的创始人突变的重要性,先前在巴基斯坦人群中报道的STS基因完全缺失,而FLG基因中的新序列变异扩展了该基因的变异谱。这些发现可用于所研究家庭的遗传咨询。
BACKGROUND: Congenital
ichthyosis is a diverse group of keratinization disorders associated with generalized scaling of skin of varying severity. The non-syndromic forms of congenital
ichthyosis are further grouped into common
ichthyosis (
ichthyosis vulgaris and X-linked
ichthyosis), autosomal recessive congenital
ichthyosis, and keratopathic
ichthyosis.
OBJECTIVE: To identify sequence variants involved in different forms of hereditary ichthyoses.
METHODS: We studied eight families with different types of
ichthyosis including four families with autosomal recessive congenital
ichthyosis and four families with common
ichthyosis. Whole exome sequencing and PCR based genotyping was carried out to find out the molecular basis of disease.
RESULTS: In one family, a novel duplication sequence variant NM_002016.2:c.2767dupT; NP_002007.1:p.Ser923PhefsTer2 was identified in FLG gene; in four families a previously reported nonsense sequence variant NM_000359.3:c.232C>T; NP_002007.1:p.Arg78Ter was identified in TGM1 gene, while, in three families of X-linked recessive ichthyosis, the whole STS gene (NM_001320752.2; NP_001307681.2) regions were deleted.
CONCLUSIONS: Gene expression studies have not been performed that would have strengthened the findings of computational analysis.
CONCLUSIONS: This study highlights the significance of the c.232C>T variant in the TGM1 gene as a possible founder mutation, complete STS gene deletion as reported previously in Pakistani population, while novel sequence variant in the FLG gene expands the spectrum of variations in this gene. These findings may be used for genetic counseling of the studied families.