Armstrong D K, McKenna K E, Hughes A E
Division of Molecular Medicine, Queen's University Belfast, Northern Ireland, UK.
J Invest Dermatol. 1998 Oct;111(4):702-4. doi: 10.1046/j.1523-1747.1998.00343.x.
A mutation in the gene encoding loricrin has recently been reported in a subset of patients with Vohwinkel's Keratoderma manifesting an associated ichthyosiform dermatosis. We have studied a further kindred with this clinical phenotype. Microsatellite marker analysis was consistent with linkage to chromosome 1q21 and direct sequencing of loricrin identified a heterozygous mutation with an insertion of a T residue at codon 209. This mutation is predicted to produce a mutant protein with a frameshift of its terminal 107 amino acids and to be 22 amino acids longer than the wild-type protein due to a delayed termination codon. The only previously reported mutation is a G insertion producing a frameshift after codon 231. The novel mutation we report is likely to have a similar functional effect on cornified envelope formation, with disturbance of transglutaminase-mediated cross-linking of envelope components, and serves to confirm the predicted role of insertional mutations in Vohwinkel's Keratoderma associated with ichthyosis.
最近有报道称，在一组表现为相关鱼鳞病样皮肤病的Vohwinkel角化病患者中，编码loricrin的基因发生了突变。我们研究了另一例具有这种临床表型的家族。微卫星标记分析结果与1q21染色体连锁一致，对loricrin进行直接测序发现了一个杂合突变，即在第209密码子处插入了一个T残基。预计该突变会产生一种突变蛋白，其末端107个氨基酸发生移码，并且由于终止密码子延迟，该蛋白比野生型蛋白长22个氨基酸。之前唯一报道的突变是在第231密码子后插入一个G导致移码。我们报道的这种新突变可能对角质包膜形成具有类似的功能影响，会干扰转谷氨酰胺酶介导的包膜成分交联，并且有助于证实插入突变在与鱼鳞病相关的Vohwinkel角化病中的预测作用。
