PDF(Pubmed)
Abstract：
Pachyonychia congenita is an uncommon autosomal dominant skin disorder characterized by hypertrophic nail dystrophy, palmoplantar keratoderma, oral leukokeratosis, and cutaneous cysts. And fissured tongue is rarely reported in patients with pachyonychia congenita. The disease is primarily associated with mutations in five keratin genes, namely KRT6A, KRT6B, KRT6C, KRT16 or KRT17. Herein we report a 9-year-old Chinese girl who has thickened nails, keratinized plaques, and fissured tongue since birth. To investigate the underlying genetic cause, whole-exome sequencing and Sanger sequencing were performed in this patient and her family members. We identified a candidate variant c.1460-2_1460del (p.S487Lfs*21) in the KRT6A gene (NM_005554.4) by whole-exome sequencing. Sanger sequencing revealed the absence of the mutation in both parents, indicating that it is a de novo variant. Thus, the novel heterozygous frameshift mutation c.1460-2_1460del (p.S487Lfs*21) within exon 9 of KRT6A was identified as the genetic cause of the patient. Our study identified a rare de novo heterozygous frameshift mutation in the KRT6A gene in a patient with pachyonychia congenita presenting fissured tongue. Our findings expand the KRT6A gene mutation spectrum of Pachyonychia congenita, and will contribute to the future genetic counseling and gene therapy for this disease.
摘要：
先天性甲癣是一种罕见的常染色体显性皮肤病，以肥厚性指甲营养不良为特征，掌plant角化病，口腔白细胞角化病，还有皮肤囊肿.先天性甲沟炎患者很少报告舌头裂开。这种疾病主要与五种角蛋白基因突变有关,即KRT6A，KRT6B,KRT6C,KRT16或KRT17。在这里，我们报道了一个9岁的中国女孩，她的指甲变厚了，角化斑块,和裂开的舌头，因为出生。为了调查潜在的遗传原因，对该患者及其家庭成员进行了全外显子组测序和Sanger测序.我们确定了一个候选变体c.1460-2_1460del（p。S487Lfs*21）在KRT6A基因（NM_005554.4）中通过全外显子组测序。Sanger测序显示父母双方都没有突变，表明它是一个从头变体。因此，新的杂合移码突变c.1460-2_1460del（p。KRT6A外显子9内的S487Lfs*21）被鉴定为患者的遗传原因。我们的研究发现了先天性假甲患者的KRT6A基因中罕见的从头杂合移码突变。我们的发现扩展了先天性假甲的KRT6A基因突变谱，并将为该疾病的未来遗传咨询和基因治疗做出贡献。
