Novel splice site mutation in the LIPH gene in a patient with autosomal recessive woolly hair/hypotrichosis: Case report and published work review
Novel splice site mutation in the LIPH gene in a patient with autosomal recessive woolly hair/hypotrichosis: Case report and published work review
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DOI：
10.1111/1346-8138.14257
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发表时间：
2018-05
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影响因子：
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通讯作者：
Y. Mizukami;R. Hayashi;D. Tsuruta;Y. Shimomura;K. Sugawara
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作者：
Y. Mizukami;R. Hayashi;D. Tsuruta;Y. Shimomura;K. Sugawara
常染色体隐性遗传羊毛状毛发是一种相对罕见的遗传性毛发疾病，其特征是稀疏、短、卷曲的毛发。已知这种情况是由LIPH基因、LPAR 6基因或KRT 25基因突变引起的。在日本人群中，大多数常染色体隐性遗传的羊毛状毛发患者携带LIPH基因中的两种创始突变之一，c.736T>A（p.Cys246Ser）或c.742C>A（p.His248Asn）。然而，偶尔，患有这种疾病的个体携带复合杂合突变，通常是一个创始人突变和另一个突变。在这项研究中，我们描述了一个病人的复合杂合突变LIPH基因在c.736T>A和c.1095 - 3C>G。后一个突变产生了一个新的剪接位点。这是LIPH基因中描述的第四个剪接位点突变。此外，我们在培养的细胞中进行了体外转录测定，并证明c.1095 - 3C>G突变导致移码，这在蛋白质水平上产生了一个提前终止密码子（p.Glu366Ilefs*7）。最后，我们总结了以前报道的LIPH基因的突变。我们的发现为常染色体隐性遗传羊毛状毛发的分子基础提供了进一步的线索。
Autosomal recessive woolly hair is a relatively rare hereditary hair disorder characterized by sparse, short, curly hair. This condition is known to be caused by mutations in the LIPH gene, LPAR6 gene or KRT25 gene. In the Japanese population, most patients with autosomal recessive woolly hair carry one of two founder mutations in the LIPH gene, c.736T>A (p.Cys246Ser) or c.742C>A (p.His248Asn). However, occasionally, individuals with this condition carry compound heterozygous mutations, typically one founder mutation and another mutation. In this study, we describe a patient with a compound heterozygous mutation in the LIPH gene at c.736T>A and c.1095‐3C>G. The latter mutation created a novel splice site. This was the fourth splice site mutation to be described in the LIPH gene. Furthermore, we performed an in vitro transcription assay in cultured cells, and demonstrated that the c.1095‐3C>G mutation led to a frame‐shift, which created a premature termination codon at the protein level (p.Glu366Ilefs*7). Finally, we summarized the mutations previously reported for the LIPH gene. Our findings provide further clues as to the molecular basis of autosomal recessive woolly hair.