Localization Of The Punctate Palmoplantar Keratodermasis Gene By A Genome-wide Scan And Searching For The Disease Gene In A Large Chinese Family

Backgrounds Punctate palmoplantar keratodermasis (MIM number: 148600) also called keratosis punctate palmoplantaris Buschke-Fischer-Brauer type. It is a rare hereditary skin disease. It was first described by Buschke and Fischer in 1910, Brauer confirmed the heredity of this dermatosis in 1913. Clinically, it is characteristics by multiple tiny punctate keratoses over the entire palmoplantar surfaces, coalescence of the punctate keratoses into a more diffuse pattern over the pressure points of the soles, and variable nail changes. The lesions usually start to develop in late childhood to adolescence, but may also start to appear up to the fifth decade in life. Generally, disease expression was more severe on the soles than on the palms, probably due to higher pressure to the soles. The onset of the disease reported previously is between ages 12 and more than 50 years. In some reports punctate PPK was associated with malignancies, such as breast cancer, prostatic carcinoma and metastatic non-small-cell carcinoma of the lung. Punctate PPK has been reported in some literatures, but the molecular basis of it is unknown. In a previous study, the keratin gene clusters on chromosomes 12 and 17 were excluded as the disease causing genes. Recently, two loci for punctate PPK were found to map to a 9.98-cM interval flanked by markers D15S534 and D15S818 on 15q22 -15q24 in three families and a 9.20-cM interval flanked by markers D8S1804 and D8S1720 on 8q24.13-8q24.21 in two Chinese families.Objectives (1) to refine the previously mapped regions and identify the disease gene locus in a four-generation Chinese family. (2) to delineate the clinical and genetic features of punctate PPK cases by the literatures from China and other countries.