De Novo Mutation in KRT1 Leads to Epidermolytic Palmoplantar Keratoderma: from Chinese Traditional Treatment to Prenatal Diagnosis Using Whole-Exome Sequencing-Plus.

Congenital skin disorders are a class of complex genetic diseases that are difficult to diagnose and treat. We developed trio whole-exome sequencing-plus (WES-plus) for detecting de novo mutations and evaluated the use of traditional Chinese medicine (TCM) for treating congenital skin disorders. In this study, we successively performed panel-based next-generation sequencing (NGS) and Trio WES-plus in a child with frequent large blisters. Panel-based NGS revealed no pathogenic mutations. Trio WES-plus for resequencing based on cutaneous keratosis of the palms and feet detected a missense mutation (c.1436T>A, p.Ile479Asn) in the coding region of KRT1 in the child but not in his parents. Following prenatal diagnosis, a healthy second baby without the mutation was born. The disease symptoms of epidermolytic palmoplantar keratoderma (EPPK) application were improved by TCM and Western medicine. Our study revealed the pathogenicity of a de novo mutation in human KRT1, which expands the mutation spectrum of EPPK. Trio WES-plus is useful for diagnosing genetic diseases and providing genetic guidance from prenatal diagnosis to treatment.

PTK7 is a molecular marker for metastasis, TNM stage, and prognosis in oral tongue squamous cell carcinoma.

The prognosis of oral tongue squamous cell carcinoma (OTSCC) is poor, and it would be beneficial to identify prognostic markers for optimization of treatment. Protein tyrosine kinase 7 (PTK7) is a receptor tyrosine kinase that is aberrantly expressed in human cancers. No exploration of the role of PTK7 in OTSCC has been reported. We detected expression of PTK7 protein in a set of tissue samples of OTSCC. The relationship between PTK7 expression and clinicopathologic parameters and overall survival of patients was analyzed. The expression level of PTK7 protein in OTSCC was increased relative to that in normal squamous cells. High expression of PTK7 was positively associated with TNM stage (p = 0.024), tumor differentiation (p = 0.019), and lymph node metastasis (p = 0.077). Patients with high expression of PTK7 had poor overall survival (p = 0.058). Our data indicate that PTK7 protein expression is associated with the prognosis of OTSCC and may serve as a therapeutic target.